Publications
2021
Scheer Hélène, Almeida Caroline, Ferrier Emilie, Simonnot Quentin, Poirier Laure, Pflieger David, Sement François M., Koechler Sandrine, Piermaria Christina, Krawczyk Paweł, Mroczek Seweryn, Chicher Johana, Kuhn Lauriane, Dziembowski Andrzej, Hammann Philippe, Zuber Hélène, Gagliardi Dominique
The TUTase URT1 connects decapping activators and prevents the accumulation of excessively deadenylated mRNAs to avoid siRNA biogenesis Article de journal
Dans: Nature Communications, vol. 12, no. 1, p. 1298, 2021, ISSN: 2041-1723.
Résumé | Liens | BibTeX | Étiquettes: Arabidopsis, Arabidopsis Proteins, Co-Repressor Proteins, DEAD-box RNA Helicases, Gene Expression Regulation, Humans, messenger, Plant, PPSE, Proto-Oncogene Proteins, Ribonucleoproteins, RNA, RNA Nucleotidyltransferases, RNA Stability, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Small Interfering, Tobacco, transcriptome, Uridine
@article{scheer_tutase_2021,
title = {The TUTase URT1 connects decapping activators and prevents the accumulation of excessively deadenylated mRNAs to avoid siRNA biogenesis},
author = {Hélène Scheer and Caroline Almeida and Emilie Ferrier and Quentin Simonnot and Laure Poirier and David Pflieger and François M. Sement and Sandrine Koechler and Christina Piermaria and Paweł Krawczyk and Seweryn Mroczek and Johana Chicher and Lauriane Kuhn and Andrzej Dziembowski and Philippe Hammann and Hélène Zuber and Dominique Gagliardi},
doi = {10.1038/s41467-021-21382-2},
issn = {2041-1723},
year = {2021},
date = {2021-02-01},
journal = {Nature Communications},
volume = {12},
number = {1},
pages = {1298},
abstract = {Uridylation is a widespread modification destabilizing eukaryotic mRNAs. Yet, molecular mechanisms underlying TUTase-mediated mRNA degradation remain mostly unresolved. Here, we report that the Arabidopsis TUTase URT1 participates in a molecular network connecting several translational repressors/decapping activators. URT1 directly interacts with DECAPPING 5 (DCP5), the Arabidopsis ortholog of human LSM14 and yeast Scd6, and this interaction connects URT1 to additional decay factors like DDX6/Dhh1-like RNA helicases. Nanopore direct RNA sequencing reveals a global role of URT1 in shaping poly(A) tail length, notably by preventing the accumulation of excessively deadenylated mRNAs. Based on in vitro and in planta data, we propose a model that explains how URT1 could reduce the accumulation of oligo(A)-tailed mRNAs both by favoring their degradation and because 3' terminal uridines intrinsically hinder deadenylation. Importantly, preventing the accumulation of excessively deadenylated mRNAs avoids the biogenesis of illegitimate siRNAs that silence endogenous mRNAs and perturb Arabidopsis growth and development.},
keywords = {Arabidopsis, Arabidopsis Proteins, Co-Repressor Proteins, DEAD-box RNA Helicases, Gene Expression Regulation, Humans, messenger, Plant, PPSE, Proto-Oncogene Proteins, Ribonucleoproteins, RNA, RNA Nucleotidyltransferases, RNA Stability, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Small Interfering, Tobacco, transcriptome, Uridine},
pubstate = {published},
tppubtype = {article}
}
2020
Mueller Christopher G, Camara Abdouramane, Flacher Vincent
[The sinusoidal microenvironment regulates the niche and the differentiation of lymph node macrophages] Article de journal
Dans: Medecine Sciences: M/S, vol. 36, no. 10, p. 835–838, 2020, ISSN: 1958-5381.
Liens | BibTeX | Étiquettes: Animals, Capillaries, Cell Differentiation, Cellular, Humans, Immunity, Lymph Nodes, Lymphatic Vessels, Macrophages, Stem Cell Niche, Team-Mueller
@article{mueller_sinusoidal_2020,
title = {[The sinusoidal microenvironment regulates the niche and the differentiation of lymph node macrophages]},
author = {Christopher G Mueller and Abdouramane Camara and Vincent Flacher},
doi = {10.1051/medsci/2020148},
issn = {1958-5381},
year = {2020},
date = {2020-01-01},
journal = {Medecine Sciences: M/S},
volume = {36},
number = {10},
pages = {835--838},
keywords = {Animals, Capillaries, Cell Differentiation, Cellular, Humans, Immunity, Lymph Nodes, Lymphatic Vessels, Macrophages, Stem Cell Niche, Team-Mueller},
pubstate = {published},
tppubtype = {article}
}
2019
Bordoni Valentina, Reina Giacomo, Orecchioni Marco, Furesi Giulia, Thiele Stefanie, Gardin Chiara, Zavan Barbara, Cuniberti Gianaurelio, Bianco Alberto, Rauner Martina, Delogu Lucia G
Stimulation of bone formation by monocyte-activator functionalized graphene oxide in vivo Article de journal
Dans: Nanoscale, vol. 11, no. 41, p. 19408–19421, 2019, ISSN: 2040-3372.
Résumé | Liens | BibTeX | Étiquettes: Animals, Biocompatible Materials, Bone Morphogenetic Protein 2, Calcium Phosphates, Cell Differentiation, Cell Survival, Coculture Techniques, Graphite, Humans, I2CT, Inbred C57BL, Male, Mesenchymal Stem Cells, Mice, Monocytes, Oncostatin M, Osteoblasts, Osteogenesis, Signal Transduction, Team-Bianco, Tibia, Wnt Proteins
@article{bordoni_stimulation_2019,
title = {Stimulation of bone formation by monocyte-activator functionalized graphene oxide in vivo},
author = {Valentina Bordoni and Giacomo Reina and Marco Orecchioni and Giulia Furesi and Stefanie Thiele and Chiara Gardin and Barbara Zavan and Gianaurelio Cuniberti and Alberto Bianco and Martina Rauner and Lucia G Delogu},
doi = {10.1039/c9nr03975a},
issn = {2040-3372},
year = {2019},
date = {2019-11-01},
journal = {Nanoscale},
volume = {11},
number = {41},
pages = {19408--19421},
abstract = {Nanosystems are able to enhance bone regeneration, a complex process requiring the mutual interplay between immune and skeletal cells. Activated monocytes can communicate pro-osteogenic signals to mesenchymal stem cells and promote osteogenesis. Thus, the activation of monocytes is a promising strategy to improve bone regeneration. Nanomaterials specifically selected to provoke immune-mediated bone formation are still missing. As a proof of concept, we apply here the intrinsic immune-characteristics of graphene oxide (GO) with the well-recognized osteoinductive capacity of calcium phosphate (CaP) in a biocompatible nanomaterial called maGO-CaP (monocytes activator GO complexed with CaP). In the presence of monocytes, the alkaline phosphatase activity and the expression of osteogenic markers increased. Studying the mechanisms of action, we detected an up-regulation of Wnt and BMP signaling, two key osteogenic pathways. The role of the immune activation was evidenced by the over-production of oncostatin M, a pro-osteogenic factor produced by monocytes. Finally, we tested the pro-osteogenic effects of maGO-CaP in vivo. maGO-CaP injected into the tibia of mice enhanced local bone mass and the bone formation rate. Our study suggests that maGO-CaP can activate monocytes to enhance osteogenesis ex vivo and in vivo.},
keywords = {Animals, Biocompatible Materials, Bone Morphogenetic Protein 2, Calcium Phosphates, Cell Differentiation, Cell Survival, Coculture Techniques, Graphite, Humans, I2CT, Inbred C57BL, Male, Mesenchymal Stem Cells, Mice, Monocytes, Oncostatin M, Osteoblasts, Osteogenesis, Signal Transduction, Team-Bianco, Tibia, Wnt Proteins},
pubstate = {published},
tppubtype = {article}
}
Mueller Christopher G, Voisin Benjamin
Of skin and bone: did Langerhans cells and osteoclasts evolve from a common ancestor? Article de journal
Dans: Journal of Anatomy, vol. 235, no. 2, p. 412–417, 2019, ISSN: 1469-7580.
Résumé | Liens | BibTeX | Étiquettes: Animals, Biological Evolution, Dendritic cell, Evolution, hair follicle, Humans, Langerhans cell, Langerhans Cells, Macrophage, OSTEOCLAST, Osteoclasts, Team-Mueller
@article{mueller_skin_2019,
title = {Of skin and bone: did Langerhans cells and osteoclasts evolve from a common ancestor?},
author = {Christopher G Mueller and Benjamin Voisin},
doi = {10.1111/joa.12543},
issn = {1469-7580},
year = {2019},
date = {2019-08-01},
journal = {Journal of Anatomy},
volume = {235},
number = {2},
pages = {412--417},
abstract = {Skin Langerhans cells are antigen-presenting cells of the interfollicular epidermis and the upper part of the hair follicle, whereas osteoclasts are specialized bone-resorbing macrophages. Although at first view these two cell types appear to have little in common, a closer analysis reveals shared features, and when taking into account their surrounding environment, a hypothesis can be developed that Langerhans cells and osteoclasts have evolved from a common ancestral cell type. In this mini-review, we have compared the ontogenetic features of Langerhans cells and osteoclasts from a genetic and a functional point of view, an issue that so far has been overlooked. The gene programs that control cell differentiation, and the body parts where they reside, present surprising similarities. Whereas the function of osteoclasts in bone degradation has been established since the first vertebrates, Langerhans cells may have undergone a stepwise adaptation from aquatic to terrestrial life. Their cell function co-evolved with the imperatives of the skin to protect against physical impact, heat, water loss and pathogens, which implied the capacity of Langerhans cells to associate with skin appendages and to develop immunostimulatory functions. For the highly versatile and efficient immune system of modern vertebrates, Langerhans cells may be a memory of the past.},
keywords = {Animals, Biological Evolution, Dendritic cell, Evolution, hair follicle, Humans, Langerhans cell, Langerhans Cells, Macrophage, OSTEOCLAST, Osteoclasts, Team-Mueller},
pubstate = {published},
tppubtype = {article}
}
Schaeffer Evelyne, Sánchez-Fernández Elena M, Gonçalves-Pereira Rita, Flacher Vincent, Lamon Delphine, Duval Monique, Fauny Jean-Daniel, Fernández José M García, Mueller Christopher G, Mellet Carmen Ortiz
sp2-Iminosugar glycolipids as inhibitors of lipopolysaccharide-mediated human dendritic cell activation in vitro and of acute inflammation in mice in vivo Article de journal
Dans: European Journal of Medicinal Chemistry, vol. 169, p. 111–120, 2019, ISSN: 1768-3254.
Résumé | Liens | BibTeX | Étiquettes: Activation, Acute Disease, Animals, antagonists & inhibitors, CD14, Cells, chemical synthesis, Chemistry, CO-RECEPTOR, Cultured, Dendritic cell, Dendritic Cells, Dose-Response Relationship, Drug, drug effects, drug therapy, Glycolipid, Glycolipids, Human, Humans, Iminosugar, immunopathology, IN VITRO, In vivo, Inbred C57BL, inflammation, Interleukin-6, lipopolysaccharide, Lipopolysaccharides, LPS, Male, Maturation, metabolism, Mice, MICROGLIA, Molecular Structure, mouse, pathology, Pharmacology, PRODUCTION, Receptor, signaling, Structure-Activity Relationship, Sulfone, Sulfoxide, Tail, target, Team-Mueller
@article{schaeffer_sp2-iminosugar_2019,
title = {sp2-Iminosugar glycolipids as inhibitors of lipopolysaccharide-mediated human dendritic cell activation in vitro and of acute inflammation in mice in vivo},
author = {Evelyne Schaeffer and Elena M Sánchez-Fernández and Rita Gonçalves-Pereira and Vincent Flacher and Delphine Lamon and Monique Duval and Jean-Daniel Fauny and José M García Fernández and Christopher G Mueller and Carmen Ortiz Mellet},
doi = {10.1016/j.ejmech.2019.02.078},
issn = {1768-3254},
year = {2019},
date = {2019-05-01},
journal = {European Journal of Medicinal Chemistry},
volume = {169},
pages = {111--120},
abstract = {Glycolipid mimetics consisting of a bicyclic polyhydroxypiperidine-cyclic carbamate core and a pseudoanomeric hydrophobic tail, termed sp2-iminosugar glycolipids (sp2-IGLs), target microglia during neuroinflammatory processes. Here we have synthesized and investigated new variants of sp2-IGLs for their ability to suppress the activation of human monocyte-derived dendritic cells (DCs) by lipopolysaccharide (LPS) signaling through Toll-like receptor 4. We report that the best lead was (1R)-1-dodecylsulfonyl-5N,6O-oxomethylidenenojirimycin (DSO2-ONJ), able to inhibit LPS-induced TNFα production and maturation of DCs. Immunovisualization experiments, using a mannoside glycolipid conjugate (MGC) that also suppress LPS-mediated DC activation as control, evidenced a distinct mode of action for the sp2-IGLs: unlike MGCs, DSO2-ONJ did not elicit internalization of the LPS co-receptor CD14 or induce its co-localization with the Toll-like receptor 4. In a mouse model of LPS-induced acute inflammation, DSO2-ONJ demonstrated anti-inflammatory activity by inhibiting the production of the pro-inflammatory interleukin-6. The ensemble of the data highlights sp2-IGLs as a promising new class of molecules against inflammation by interfering in Toll-like receptor intracellular signaling.},
keywords = {Activation, Acute Disease, Animals, antagonists & inhibitors, CD14, Cells, chemical synthesis, Chemistry, CO-RECEPTOR, Cultured, Dendritic cell, Dendritic Cells, Dose-Response Relationship, Drug, drug effects, drug therapy, Glycolipid, Glycolipids, Human, Humans, Iminosugar, immunopathology, IN VITRO, In vivo, Inbred C57BL, inflammation, Interleukin-6, lipopolysaccharide, Lipopolysaccharides, LPS, Male, Maturation, metabolism, Mice, MICROGLIA, Molecular Structure, mouse, pathology, Pharmacology, PRODUCTION, Receptor, signaling, Structure-Activity Relationship, Sulfone, Sulfoxide, Tail, target, Team-Mueller},
pubstate = {published},
tppubtype = {article}
}
Rauti Rossana, Medelin Manuela, Newman Leon, Vranic Sandra, Reina Giacomo, Bianco Alberto, Prato Maurizio, Kostarelos Kostas, Ballerini Laura
Graphene Oxide Flakes Tune Excitatory Neurotransmission in Vivo by Targeting Hippocampal Synapses Article de journal
Dans: Nano Letters, vol. 19, no. 5, p. 2858–2870, 2019, ISSN: 1530-6992.
Résumé | Liens | BibTeX | Étiquettes: Animals, Excitatory Amino Acid Agents, glutamate, Glutamic Acid, graphene, Graphite, hippocampal network, Hippocampus, Humans, I2CT, Nanostructures, Neurodegenerative Diseases, Neurons, Newborn, Primary Cell Culture, quantum dots, Rats, synapses, Synaptic Transmission, Team-Bianco, Wistar
@article{rauti_graphene_2019,
title = {Graphene Oxide Flakes Tune Excitatory Neurotransmission in Vivo by Targeting Hippocampal Synapses},
author = {Rossana Rauti and Manuela Medelin and Leon Newman and Sandra Vranic and Giacomo Reina and Alberto Bianco and Maurizio Prato and Kostas Kostarelos and Laura Ballerini},
doi = {10.1021/acs.nanolett.8b04903},
issn = {1530-6992},
year = {2019},
date = {2019-01-01},
journal = {Nano Letters},
volume = {19},
number = {5},
pages = {2858--2870},
abstract = {Synapses compute and transmit information to connect neural circuits and are at the basis of brain operations. Alterations in their function contribute to a vast range of neuropsychiatric and neurodegenerative disorders and synapse-based therapeutic intervention, such as selective inhibition of synaptic transmission, may significantly help against serious pathologies. Graphene is a two-dimensional nanomaterial largely exploited in multiple domains of science and technology, including biomedical applications. In hippocampal neurons in culture, small graphene oxide nanosheets (s-GO) selectively depress glutamatergic activity without altering cell viability. Glutamate is the main excitatory neurotransmitter in the central nervous system and growing evidence suggests its involvement in neuropsychiatric disorders. Here we demonstrate that s-GO directly targets the release of presynaptic vesicle. We propose that s-GO flakes reduce the availability of transmitter, via promoting its fast release and subsequent depletion, leading to a decline ofglutamatergic neurotransmission. We injected s-GO in the hippocampus in vivo, and 48 h after surgery ex vivo patch-clamp recordings from brain slices show a significant reduction in glutamatergic synaptic activity in respect to saline injections.},
keywords = {Animals, Excitatory Amino Acid Agents, glutamate, Glutamic Acid, graphene, Graphite, hippocampal network, Hippocampus, Humans, I2CT, Nanostructures, Neurodegenerative Diseases, Neurons, Newborn, Primary Cell Culture, quantum dots, Rats, synapses, Synaptic Transmission, Team-Bianco, Wistar},
pubstate = {published},
tppubtype = {article}
}
Ji Ding-Kun, Ménard-Moyon Cécilia, Bianco Alberto
Physically-triggered nanosystems based on two-dimensional materials for cancer theranostics Article de journal
Dans: Advanced Drug Delivery Reviews, vol. 138, p. 211–232, 2019, ISSN: 1872-8294.
Résumé | Liens | BibTeX | Étiquettes: 2D Materials, Animals, Diagnosis, graphene, Graphite, Humans, I2CT, Light, Magnetic Fields, Nanomaterials, Nanostructures, Neoplasms, Team-Bianco, Theragnosis, Theranostic Nanomedicine, therapy
@article{ji_physically-triggered_2019,
title = {Physically-triggered nanosystems based on two-dimensional materials for cancer theranostics},
author = {Ding-Kun Ji and Cécilia Ménard-Moyon and Alberto Bianco},
doi = {10.1016/j.addr.2018.08.010},
issn = {1872-8294},
year = {2019},
date = {2019-01-01},
journal = {Advanced Drug Delivery Reviews},
volume = {138},
pages = {211--232},
abstract = {There is an increasing demand to develop effective methods for treating malignant diseases to improve healthcare in our society. Stimuli-responsive nanosystems, which can respond to internal or external stimuli are promising in cancer therapy and diagnosis due to their functionality and versatility. As a newly emerging class of nanomaterials, two-dimensional (2D) nanomaterials have attracted huge interest in many different fields including biomedicine due to their unique physical and chemical properties. In the past decade, stimuli-responsive nanosystems based on 2D nanomaterials have been widely studied, showing promising applications in cancer therapy and diagnosis, including phototherapies, magnetic therapy, drug and gene delivery, and non-invasive imaging. Here, we will focus our attention on the state-of-the-art of physically-triggered nanosystems based on graphene and two-dimensional nanomaterials for cancer therapy and diagnosis. The physical triggers include light, temperature, magnetic and electric fields.},
keywords = {2D Materials, Animals, Diagnosis, graphene, Graphite, Humans, I2CT, Light, Magnetic Fields, Nanomaterials, Nanostructures, Neoplasms, Team-Bianco, Theragnosis, Theranostic Nanomedicine, therapy},
pubstate = {published},
tppubtype = {article}
}
2018
Reynard Olivier, Schaeffer Evelyne, Volchkova Valentina A, Cimarelli Andrea, Mueller Christopher G, Volchkov Viktor E
Mannoside Glycolipid Conjugates Display Antiviral Activity Against Ebola Virus Article de journal
Dans: The Journal of Infectious Diseases, vol. 218, no. suppl_5, p. S666–S671, 2018, ISSN: 1537-6613.
Résumé | Liens | BibTeX | Étiquettes: Animals, Antiviral Agents, Chlorocebus aethiops, Ebolavirus, Glycolipids, Humans, Mannosides, Team-Mueller, Vero Cells, Virus Internalization
@article{reynard_mannoside_2018,
title = {Mannoside Glycolipid Conjugates Display Antiviral Activity Against Ebola Virus},
author = {Olivier Reynard and Evelyne Schaeffer and Valentina A Volchkova and Andrea Cimarelli and Christopher G Mueller and Viktor E Volchkov},
doi = {10.1093/infdis/jiy464},
issn = {1537-6613},
year = {2018},
date = {2018-11-01},
journal = {The Journal of Infectious Diseases},
volume = {218},
number = {suppl_5},
pages = {S666--S671},
abstract = {The West African outbreak of Ebola virus (EBOV) infection during 2013-2016 highlighted the need for development of field-applicable therapeutic drugs for this infection. Here we report that mannoside glycolipid conjugates (MGCs) consisting of a trimannose head and a lipophilic chain assembled by a linker inhibit EBOV infection not only of human monocyte-derived dendritic cells and macrophages, but also of a number of susceptible cells. Analysis of the mode of action leads us to conclude that MGCs act directly on cells, notably by preventing virus endocytosis.},
keywords = {Animals, Antiviral Agents, Chlorocebus aethiops, Ebolavirus, Glycolipids, Humans, Mannosides, Team-Mueller, Vero Cells, Virus Internalization},
pubstate = {published},
tppubtype = {article}
}
Sawaf Matthieu, Fauny Jean-Daniel, Felten Renaud, Sagez Flora, Gottenberg Jacques-Eric, Dumortier Hélène, Monneaux Fanny
Defective BTLA functionality is rescued by restoring lipid metabolism in lupus CD4+ Ŧ cells Article de journal
Dans: JCI insight, vol. 3, no. 13, 2018, ISSN: 2379-3708.
Résumé | Liens | BibTeX | Étiquettes: 80 and over, Adolescent, Adult, Aged, Autoimmune Diseases, Autoimmunity, CD4-Positive T-Lymphocytes, Cell Proliferation, CTLA-4 Antigen, Dumortier, Female, France, Humans, I2CT, Imagerie, Immunologic, Immunology, Lipid Metabolism, lupus, Lupus Erythematosus, Lymphocyte Activation, Male, Middle Aged, Monneaux, Programmed Cell Death 1 Receptor, Receptors, Signal Transduction, Systemic, Team-Dumortier, Young Adult
@article{sawaf_defective_2018,
title = {Defective BTLA functionality is rescued by restoring lipid metabolism in lupus CD4+ Ŧ cells},
author = {Matthieu Sawaf and Jean-Daniel Fauny and Renaud Felten and Flora Sagez and Jacques-Eric Gottenberg and Hélène Dumortier and Fanny Monneaux},
doi = {10.1172/jci.insight.99711},
issn = {2379-3708},
year = {2018},
date = {2018-01-01},
journal = {JCI insight},
volume = {3},
number = {13},
abstract = {Coinhibitory receptors play an important role in the prevention of autoimmune diseases, such as systemic lupus erythematosus (SLE), by limiting T cell activation. B and T lymphocyte attenuator (BTLA) is an inhibitory receptor, similar to cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD1), that negatively regulates the immune response. The role of BTLA in the pathogenesis of autoimmune diseases in humans and, more specifically, in SLE is largely unknown. We investigated BTLA expression on various T cell subsets, and we did not observe significant variations of BTLA expression between lupus patients and healthy controls. However, the enhancement of BTLA expression after activation was significantly lower in SLE patients compared with that in healthy controls. Furthermore, we found an impaired capacity of BTLA to inhibit T cell activation in SLE due to a poor BTLA recruitment to the immunological synapse following T cell stimulation. Finally, we demonstrated that defective BTLA function can be corrected by restoring intracellular trafficking and by normalizing the lipid metabolism in lupus CD4+ T cells. Collectively, our results evidence that the BTLA signaling pathway is altered in SLE T cells and highlight the potential of targeting this pathway for the development of new therapeutic strategies in lupus.},
keywords = {80 and over, Adolescent, Adult, Aged, Autoimmune Diseases, Autoimmunity, CD4-Positive T-Lymphocytes, Cell Proliferation, CTLA-4 Antigen, Dumortier, Female, France, Humans, I2CT, Imagerie, Immunologic, Immunology, Lipid Metabolism, lupus, Lupus Erythematosus, Lymphocyte Activation, Male, Middle Aged, Monneaux, Programmed Cell Death 1 Receptor, Receptors, Signal Transduction, Systemic, Team-Dumortier, Young Adult},
pubstate = {published},
tppubtype = {article}
}
Fadeel Bengt, Bussy Cyrill, Merino Sonia, Vázquez Ester, Flahaut Emmanuel, Mouchet Florence, Evariste Lauris, Gauthier Laury, Koivisto Antti J, Vogel Ulla, Martín Cristina, Delogu Lucia G, Buerki-Thurnherr Tina, Wick Peter, Beloin-Saint-Pierre Didier, Hischier Roland, Pelin Marco, Carniel Fabio Candotto, Tretiach Mauro, Cesca Fabrizia, Benfenati Fabio, Scaini Denis, Ballerini Laura, Kostarelos Kostas, Prato Maurizio, Bianco Alberto
Safety Assessment of Graphene-Based Materials: Focus on Human Health and the Environment Article de journal
Dans: ACS nano, vol. 12, no. 11, p. 10582–10620, 2018, ISSN: 1936-086X.
Résumé | Liens | BibTeX | Étiquettes: Animals, carbon nanomaterials, environment, Environmental Monitoring, Exposure, graphene, Graphite, hazard, Health, Humans, I2CT, life cycle assessment, Materials Testing, Nanostructures, Risk Assessment, safety, Structure-Activity Relationship, Team-Bianco, Toxicity
@article{fadeel_safety_2018,
title = {Safety Assessment of Graphene-Based Materials: Focus on Human Health and the Environment},
author = {Bengt Fadeel and Cyrill Bussy and Sonia Merino and Ester Vázquez and Emmanuel Flahaut and Florence Mouchet and Lauris Evariste and Laury Gauthier and Antti J Koivisto and Ulla Vogel and Cristina Martín and Lucia G Delogu and Tina Buerki-Thurnherr and Peter Wick and Didier Beloin-Saint-Pierre and Roland Hischier and Marco Pelin and Fabio Candotto Carniel and Mauro Tretiach and Fabrizia Cesca and Fabio Benfenati and Denis Scaini and Laura Ballerini and Kostas Kostarelos and Maurizio Prato and Alberto Bianco},
doi = {10.1021/acsnano.8b04758},
issn = {1936-086X},
year = {2018},
date = {2018-01-01},
journal = {ACS nano},
volume = {12},
number = {11},
pages = {10582--10620},
abstract = {Graphene and its derivatives are heralded as "miracle" materials with manifold applications in different sectors of society from electronics to energy storage to medicine. The increasing exploitation of graphene-based materials (GBMs) necessitates a comprehensive evaluation of the potential impact of these materials on human health and the environment. Here, we discuss synthesis and characterization of GBMs as well as human and environmental hazard assessment of GBMs using in vitro and in vivo model systems with the aim to understand the properties that underlie the biological effects of these materials; not all GBMs are alike, and it is essential that we disentangle the structure-activity relationships for this class of materials.},
keywords = {Animals, carbon nanomaterials, environment, Environmental Monitoring, Exposure, graphene, Graphite, hazard, Health, Humans, I2CT, life cycle assessment, Materials Testing, Nanostructures, Risk Assessment, safety, Structure-Activity Relationship, Team-Bianco, Toxicity},
pubstate = {published},
tppubtype = {article}
}
Arosio Paolo, Comito Giuseppina, Orsini Francesco, Lascialfari Alessandro, Chiarugi Paola, Ménard-Moyon Cécilia, Nativi Cristina, Richichi Barbara
Conjugation of a GM3 lactone mimetic on carbon nanotubes enhances the related inhibition of melanoma-associated metastatic events Article de journal
Dans: Organic & Biomolecular Chemistry, vol. 16, no. 33, p. 6086–6095, 2018, ISSN: 1477-0539.
Résumé | Liens | BibTeX | Étiquettes: Antineoplastic Agents, Biomimetic Materials, carbon, Cell Line, G(M3) Ganglioside, Humans, I2CT, Melanoma, Models, Molecular, Molecular Conformation, Nanotubes, Neoplasm Metastasis, Team-Bianco, tumor
@article{arosio_conjugation_2018,
title = {Conjugation of a GM3 lactone mimetic on carbon nanotubes enhances the related inhibition of melanoma-associated metastatic events},
author = {Paolo Arosio and Giuseppina Comito and Francesco Orsini and Alessandro Lascialfari and Paola Chiarugi and Cécilia Ménard-Moyon and Cristina Nativi and Barbara Richichi},
doi = {10.1039/c8ob01817k},
issn = {1477-0539},
year = {2018},
date = {2018-01-01},
journal = {Organic & Biomolecular Chemistry},
volume = {16},
number = {33},
pages = {6086--6095},
abstract = {GM3-ganglioside is known to be involved in melanoma proliferation. In order to modulate metastatic-related events, we have functionalized multi-walled carbon nanotubes (MWCNTs) with multiple copies of a GM3-lactone mimetic. The MWCNTs proved to guarantee the appropriate spatial arrangement of the mimetic allowing a stronger inhibition of migration and invasiveness of human melanoma (A375) cells compared to other multivalent constructs reported before. In addition, the effect of the multivalent tubular conjugate on the inhibition of specific tyrosine kinases, which are associated with the ganglioside complexes within the membrane domains, was demonstrated. Finally, the short-term fate of the conjugate was assessed, for the first time, by means of the 1H NMR relaxometry technique by exploiting the signal arising from the CNTs.},
keywords = {Antineoplastic Agents, Biomimetic Materials, carbon, Cell Line, G(M3) Ganglioside, Humans, I2CT, Melanoma, Models, Molecular, Molecular Conformation, Nanotubes, Neoplasm Metastasis, Team-Bianco, tumor},
pubstate = {published},
tppubtype = {article}
}
Schaeffer Evelyne, Flacher Vincent, Neuberg Patrick, Hoste Astrid, Brulefert Adrien, Fauny Jean-Daniel, Wagner Alain, Mueller Christopher G
Inhibition of dengue virus infection by mannoside glycolipid conjugates Article de journal
Dans: Antiviral Research, vol. 154, p. 116–123, 2018, ISSN: 1872-9096.
Résumé | Liens | BibTeX | Étiquettes: Animals, Antiviral Agents, Cell Line, Cell Membrane, Chemistry, Chlorocebus aethiops, Dendritic Cells, Dengue, Dengue virus, development, Drug, Drug Discovery, Flavivirus, function, Fusion, Glycolipids, Health, Hep G2 Cells, Human, Humans, immunopathology, infection, inhibition, inhibitors, Inhibitory Concentration 50, lipid, Macrophages, Mannosides, Membrane, Serogroup, Skin, Team-Mueller, vaccine, Vaccines, Vero Cells, viral Infection, virus, Virus Replication
@article{schaeffer_inhibition_2018b,
title = {Inhibition of dengue virus infection by mannoside glycolipid conjugates},
author = {Evelyne Schaeffer and Vincent Flacher and Patrick Neuberg and Astrid Hoste and Adrien Brulefert and Jean-Daniel Fauny and Alain Wagner and Christopher G Mueller},
doi = {10.1016/j.antiviral.2018.04.005},
issn = {1872-9096},
year = {2018},
date = {2018-01-01},
journal = {Antiviral Research},
volume = {154},
pages = {116--123},
abstract = {Dengue virus (DENV), a mosquito-borne flavivirus, causes severe and potentially fatal symptoms in millions of infected individuals each year. Although dengue fever represents a major global public health problem, the vaccines or antiviral drugs proposed so far have not shown sufficient efficacy and safety, calling for new antiviral developments. Here we have shown that a mannoside glycolipid conjugate (MGC) bearing a trimannose head with a saturated lipid chain inhibited DENV productive infection. It showed remarkable cell promiscuity, being active in human skin dendritic cells, hepatoma cell lines and Vero cells, and was active against all four DENV serotypes, with an IC50 in the low micromolar range. Time-of-addition experiments and structure-activity analyses revealed the importance of the lipid chain to interfere with an early viral infection step. This, together with a correlation between antiviral activity and membrane polarization by the lipid moiety indicated that the inhibitor functions by blocking viral envelope fusion with the endosome membrane. These finding establish MGCs as a novel class of antivirals against the DENV.},
keywords = {Animals, Antiviral Agents, Cell Line, Cell Membrane, Chemistry, Chlorocebus aethiops, Dendritic Cells, Dengue, Dengue virus, development, Drug, Drug Discovery, Flavivirus, function, Fusion, Glycolipids, Health, Hep G2 Cells, Human, Humans, immunopathology, infection, inhibition, inhibitors, Inhibitory Concentration 50, lipid, Macrophages, Mannosides, Membrane, Serogroup, Skin, Team-Mueller, vaccine, Vaccines, Vero Cells, viral Infection, virus, Virus Replication},
pubstate = {published},
tppubtype = {article}
}
Muller Quentin, Beaudet Marie-Josée, Serres-Bérard Thiéry De, Bellenfant Sabrina, Flacher Vincent, Berthod François
Development of an innervated tissue-engineered skin with human sensory neurons and Schwann cells differentiated from iPS cells Article de journal
Dans: Acta Biomaterialia, vol. 82, p. 93–101, 2018, ISSN: 1878-7568.
Résumé | Liens | BibTeX | Étiquettes: atopic dermatitis, Axonal migration, Biological, Canada, Cells, CGRP, Chemistry, COLLAGEN, Culture, Dermatitis, development, disease, Endothelial Cells, ENDOTHELIAL-CELLS, Epidermis, Expression, Fibroblast, Fibroblasts, function, Human, Humans, Immune System, Immunology, immunopathology, IN VITRO, Induced Pluripotent Stem Cells, inflammation, INNERVATION, Maturation, migration, Models, mouse, murine, Nerve, Neurites, Neurogenic Inflammation, Neurons, NEUROPEPTIDE, Neuropeptides, physiopathology, Pluripotent Stem Cells, Psoriasis, SCHWANN CELLS, Sensory Receptor Cells, Skin, skin disease, Skin Diseases, stem, Stem Cells, SUBSTANCE, SUBSTANCE P, Team-Mueller, Tissue Engineering, TRPV1
@article{muller_development_2018,
title = {Development of an innervated tissue-engineered skin with human sensory neurons and Schwann cells differentiated from iPS cells},
author = {Quentin Muller and Marie-Josée Beaudet and Thiéry De Serres-Bérard and Sabrina Bellenfant and Vincent Flacher and François Berthod},
doi = {10.1016/j.actbio.2018.10.011},
issn = {1878-7568},
year = {2018},
date = {2018-01-01},
journal = {Acta Biomaterialia},
volume = {82},
pages = {93--101},
abstract = {Cutaneous innervation is increasingly recognized as a major element of skin physiopathology through the neurogenic inflammation driven by neuropeptides that are sensed by endothelial cells and the immune system. To investigate this process in vitro, models of innervated tissue-engineered skin (TES) were developed, yet exclusively with murine sensory neurons extracted from dorsal root ganglions. In order to build a fully human model of innervated TES, we used induced pluripotent stem cells (iPSC) generated from human skin fibroblasts. Nearly 100% of the iPSC differentiated into sensory neurons were shown to express the neuronal markers BRN3A and β3-tubulin after 19 days of maturation. In addition, these cells were also positive to TRPV1 and neurofilament M, and some of them expressed Substance P, TrkA and TRPA1. When stimulated with molecules inducing neuropeptide release, iPSC-derived neurons released Substance P and CGRP, both in conventional monolayer culture and after seeding in a 3D fibroblast-populated collagen sponge model. Schwann cells, the essential partners of neurons for function and axonal migration, were also successfully differentiated from human iPSC as shown by their expression of the markers S100, GFAP, p75 and SOX10. When cultured for one additional month in the TES model, iPSC-derived neurons seeded at the bottom of the sponge formed a network of neurites spanning the whole TES up to the epidermis, but only when combined with mouse or iPSC-derived Schwann cells. This unique model of human innervated TES should be highly useful for the study of cutaneous neuroinflammation. STATEMENT OF SIGNIFICANCE: The purpose of this work was to develop in vitro an innovative fully human tissue-engineered skin enabling the investigation of the influence of cutaneous innervation on skin pathophysiology. To reach that aim, neurons were differentiated from human induced pluripotent stem cells (iPSCs) generated from normal human skin fibroblasts. This innervated tissue-engineered skin model will be the first one to show iPSC-derived neurons can be successfully used to build a 3D nerve network in vitro. Since innervation has been recently recognized to play a central role in many human skin diseases, such as psoriasis and atopic dermatitis, this construct promises to be at the forefront to model these diseases while using patient-derived cells.},
keywords = {atopic dermatitis, Axonal migration, Biological, Canada, Cells, CGRP, Chemistry, COLLAGEN, Culture, Dermatitis, development, disease, Endothelial Cells, ENDOTHELIAL-CELLS, Epidermis, Expression, Fibroblast, Fibroblasts, function, Human, Humans, Immune System, Immunology, immunopathology, IN VITRO, Induced Pluripotent Stem Cells, inflammation, INNERVATION, Maturation, migration, Models, mouse, murine, Nerve, Neurites, Neurogenic Inflammation, Neurons, NEUROPEPTIDE, Neuropeptides, physiopathology, Pluripotent Stem Cells, Psoriasis, SCHWANN CELLS, Sensory Receptor Cells, Skin, skin disease, Skin Diseases, stem, Stem Cells, SUBSTANCE, SUBSTANCE P, Team-Mueller, Tissue Engineering, TRPV1},
pubstate = {published},
tppubtype = {article}
}
Mueller C G, Nayar S, Campos J, Barone F
Molecular and Cellular Requirements for the Assembly of Tertiary Lymphoid Structures Article de journal
Dans: Advances in Experimental Medicine and Biology, vol. 1060, p. 55–72, 2018, ISSN: 0065-2598.
Résumé | Liens | BibTeX | Étiquettes: Animals, CCL21, CXCL13, Endothelial and stromal cells, Humans, Lymphotoxin, Molecular Targeted Therapy, RANKL, Sjögren’s syndrome, Team-Mueller, Tertiary lymphoid structures, TNF
@article{mueller_molecular_2018,
title = {Molecular and Cellular Requirements for the Assembly of Tertiary Lymphoid Structures},
author = {C G Mueller and S Nayar and J Campos and F Barone},
doi = {10.1007/978-3-319-78127-3_4},
issn = {0065-2598},
year = {2018},
date = {2018-01-01},
journal = {Advances in Experimental Medicine and Biology},
volume = {1060},
pages = {55--72},
abstract = {At sites of chronic inflammation, recruited immune cells form structures that resemble secondary lymphoid organs (SLOs). Those are characterized by segregated areas of prevalent T- or B-cell aggregation, differentiation of high endothelial venules (HEVs) and local activation of resident stromal cells. B-cell proliferation and affinity maturation towards locally displayed autoantigens have been demonstrated at those sites, known as tertiary lymphoid structures (TLSs). TLS formation has been associated with local disease persistence and progression as well as increased systemic manifestations. While bearing a similar histological structure to SLO, the signals that regulate TLS and SLO formation can diverge, and a series of pro-inflammatory cytokines has been ascribed as responsible for TLS formation at different anatomical sites. Here we review the structural elements as well as the signals responsible for TLS aggregation, aiming to provide an overview to this complex immunological phenomenon.},
keywords = {Animals, CCL21, CXCL13, Endothelial and stromal cells, Humans, Lymphotoxin, Molecular Targeted Therapy, RANKL, Sjögren’s syndrome, Team-Mueller, Tertiary lymphoid structures, TNF},
pubstate = {published},
tppubtype = {article}
}
Mueller Christopher George, Nayar Saba, Gardner David, Barone Francesca
Cellular and Vascular Components of Tertiary Lymphoid Structures Article de journal
Dans: Methods in Molecular Biology (Clifton, N.J.), vol. 1845, p. 17–30, 2018, ISSN: 1940-6029.
Résumé | Liens | BibTeX | Étiquettes: Animals, Biomarkers, CCL21, Cell Survival, Cellular Microenvironment, CXCL13, Cytokines, Humans, Immunity, inflammation, Innate, LYMPHATIC VESSEL, Lymphocyte, Lymphocyte Subsets, Lymphotoxin, Multigene Family, Neovascularization, Pathologic, Receptors, Signal Transduction, Sjögren’s syndrome, Stromal cell, Team-Mueller, Tertiary lymphoid organ, Tertiary lymphoid structures, TNF-α, Tumor Necrosis Factor
@article{mueller_cellular_2018,
title = {Cellular and Vascular Components of Tertiary Lymphoid Structures},
author = {Christopher George Mueller and Saba Nayar and David Gardner and Francesca Barone},
doi = {10.1007/978-1-4939-8709-2_2},
issn = {1940-6029},
year = {2018},
date = {2018-01-01},
journal = {Methods in Molecular Biology (Clifton, N.J.)},
volume = {1845},
pages = {17--30},
abstract = {Inflammatory immune cells recruited at the site of chronic inflammation form structures that resemble secondary lymphoid organs (SLO). These are characterized by segregated areas of prevalent T- or B-cell aggregation, differentiation of high endothelial venules, and local activation of resident stromal cells, including lymphatic endothelial cells. B-cell proliferation and affinity maturation toward locally displayed autoantigens have been demonstrated at these sites, known as tertiary lymphoid structures (TLS). TLS formation during chronic inflammation has been associated with local disease persistence and progression, as well as increased systemic manifestations. While bearing a similar histological structure to SLO, the signals that regulate TLS and SLO formation can diverge and a series of pro-inflammatory cytokines have been ascribed as responsible for TLS formation at different anatomical sites. Moreover, for a long time the structural compartment that regulates TLS homeostasis, including survival and recirculation of leucocytes has been neglected. In this chapter, we summarize the novel data available on TLS formation, structural organization, and the functional and anatomical links connecting TLS and SLOs.},
keywords = {Animals, Biomarkers, CCL21, Cell Survival, Cellular Microenvironment, CXCL13, Cytokines, Humans, Immunity, inflammation, Innate, LYMPHATIC VESSEL, Lymphocyte, Lymphocyte Subsets, Lymphotoxin, Multigene Family, Neovascularization, Pathologic, Receptors, Signal Transduction, Sjögren’s syndrome, Stromal cell, Team-Mueller, Tertiary lymphoid organ, Tertiary lymphoid structures, TNF-α, Tumor Necrosis Factor},
pubstate = {published},
tppubtype = {article}
}
2017
Chypre Mélanie, Madel Maria-Bernadette, Chaloin Olivier, Blin-Wakkach Claudine, Morice Christophe, Mueller Christopher G
Porphyrin Derivatives Inhibit the Interaction between Receptor Activator of NF-κB and Its Ligand Article de journal
Dans: ChemMedChem, vol. 12, no. 20, p. 1697–1702, 2017, ISSN: 1860-7187.
Résumé | Liens | BibTeX | Étiquettes: Animals, Cell Survival, cell-based assays, ELISA, Humans, Jurkat Cells, Mice, Molecular Structure, Osteoclasts, Osteogenesis, porphyrins, Protein Binding, RANK ligand, receptor activator of NF-κB, Receptor Activator of Nuclear Factor-kappa B, Structure-Activity Relationship, Team-Mueller
@article{chypre_porphyrin_2017,
title = {Porphyrin Derivatives Inhibit the Interaction between Receptor Activator of NF-κB and Its Ligand},
author = {Mélanie Chypre and Maria-Bernadette Madel and Olivier Chaloin and Claudine Blin-Wakkach and Christophe Morice and Christopher G Mueller},
doi = {10.1002/cmdc.201700462},
issn = {1860-7187},
year = {2017},
date = {2017-10-01},
journal = {ChemMedChem},
volume = {12},
number = {20},
pages = {1697--1702},
abstract = {Receptor activator of NF-κB (RANK), a member of the TNF-receptor superfamily, plays an important role in bone resorption and stimulates immune and epithelial cell activation. Denosumab, a human monoclonal antibody that blocks the RANK ligand (RANKL), is approved for the treatment of osteoporosis and bone metastasis. However, a small molecule that inhibits the RANK-RANKL interaction would be beneficial to decrease cost and to facilitate treatments with orally available therapeutic agents. Herein we report the discovery of the first nonpeptidic inhibitors of RANK-RANKL interactions. In screening a chemical library by competitive ELISA, the porphyrin verteporfin was identified as a hit. Derivatives were screened, and the chlorin-macrocycle-containing pheophorbide A and purpurin 18 were found to bind recombinant RANKL, to inhibit RANK-RANKL interactions in the ELISA, and to suppress the RANKL-dependent activation of model cells and the differentiation of RANK-expressing precursors into osteoclasts. This discovery of a family of small molecules that inhibit RANK activation presents an initial basis for further development of nonpeptidic therapeutic agents targeting the interaction between RANK and RANKL.},
keywords = {Animals, Cell Survival, cell-based assays, ELISA, Humans, Jurkat Cells, Mice, Molecular Structure, Osteoclasts, Osteogenesis, porphyrins, Protein Binding, RANK ligand, receptor activator of NF-κB, Receptor Activator of Nuclear Factor-kappa B, Structure-Activity Relationship, Team-Mueller},
pubstate = {published},
tppubtype = {article}
}
Gies Vincent, Wagner Alain, Seifert Cécile, Guffroy Aurélien, Fauny Jean-D., Knapp Anne-M., Pasquali Jean-L., Martin Thierry, Dumortier Hélène, Korganow Anne-S., Soulas-Sprauel Pauline
Identification of autoreactive B cells with labeled nucleosomes Article de journal
Dans: Scientific Reports, vol. 7, no. 1, p. 602, 2017, ISSN: 2045-2322.
Résumé | Liens | BibTeX | Étiquettes: Animals, Autoantibodies, Autoantigens, Autoimmunity, B-Lymphocytes, Biomarkers, Cell Line, Dumortier, Female, Flow Cytometry, Humans, I2CT, Lupus Erythematosus, Mice, Nucleosomes, Staining and Labeling, Systemic, Team-Dumortier
@article{gies_identification_2017b,
title = {Identification of autoreactive B cells with labeled nucleosomes},
author = {Vincent Gies and Alain Wagner and Cécile Seifert and Aurélien Guffroy and Jean-D. Fauny and Anne-M. Knapp and Jean-L. Pasquali and Thierry Martin and Hélène Dumortier and Anne-S. Korganow and Pauline Soulas-Sprauel},
doi = {10.1038/s41598-017-00664-0},
issn = {2045-2322},
year = {2017},
date = {2017-01-01},
journal = {Scientific Reports},
volume = {7},
number = {1},
pages = {602},
abstract = {The pathogenesis of autoimmune diseases has not been completely elucidated yet, and only a few specific treatments have been developed so far. In autoimmune diseases mediated by pathogenic autoantibodies, such as systemic lupus erythematosus, the specific detection and analysis of autoreactive B cells is crucial for a better understanding of the physiopathology. Biological characterization of these cells may help to define new therapeutic targets. Very few techniques allowing the precise detection of autoreactive B cells have been described so far. Herein we propose a new flow cytometry technique for specific detection of anti-nucleosome B cells, which secrete autoantibodies in systemic lupus erythematosus, using labeled nucleosomes. We produced different fluorochrome-labeled nucleosomes, characterized them, and finally tested them in flow cytometry. Nucleosomes labeled via the cysteines present in H3 histone specifically bind to autoreactive B cells in the anti-DNA transgenic B6.56R mice model. The present work validates the use of fluorochrome-labeled nucleosomes via cysteines to identify anti-nucleosome B cells and offers new opportunities for the description of autoreactive B cell phenotype.},
keywords = {Animals, Autoantibodies, Autoantigens, Autoimmunity, B-Lymphocytes, Biomarkers, Cell Line, Dumortier, Female, Flow Cytometry, Humans, I2CT, Lupus Erythematosus, Mice, Nucleosomes, Staining and Labeling, Systemic, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
Russier Julie, León Verónica, Orecchioni Marco, Hirata Eri, Virdis Patrizia, Fozza Claudio, Sgarrella Francesco, Cuniberti Gianaurelio, Prato Maurizio, Vázquez Ester, Bianco Alberto, Delogu Lucia G
Few-Layer Graphene Kills Selectively Tumor Cells from Myelomonocytic Leukemia Patients Article de journal
Dans: Angewandte Chemie (International Ed. in English), vol. 56, no. 11, p. 3014–3019, 2017, ISSN: 1521-3773.
Résumé | Liens | BibTeX | Étiquettes: Acute, cancer therapy, Chronic, Cultured, graphene, Graphite, Humans, I2CT, Immune System, leukemia, Leukocytes, Mononuclear, Myeloid, Myelomonocytic, myelomonocytic leukemia, Nanomaterials, Particle Size, Surface Properties, Team-Bianco, Tumor Cells
@article{russier_few-layer_2017,
title = {Few-Layer Graphene Kills Selectively Tumor Cells from Myelomonocytic Leukemia Patients},
author = {Julie Russier and Verónica León and Marco Orecchioni and Eri Hirata and Patrizia Virdis and Claudio Fozza and Francesco Sgarrella and Gianaurelio Cuniberti and Maurizio Prato and Ester Vázquez and Alberto Bianco and Lucia G Delogu},
doi = {10.1002/anie.201700078},
issn = {1521-3773},
year = {2017},
date = {2017-01-01},
journal = {Angewandte Chemie (International Ed. in English)},
volume = {56},
number = {11},
pages = {3014--3019},
abstract = {In the cure of cancer, a major cause of today's mortality, chemotherapy is the most common treatment, though serious frequent challenges are encountered by current anticancer drugs. We discovered that few-layer graphene (FLG) dispersions have a specific killer action on monocytes, showing neither toxic nor activation effects on other immune cells. We confirmed the therapeutic application of graphene on an aggressive type of cancer that is myelomonocytic leukemia, where the monocytes are in their malignant form. We demonstrated that graphene has the unique ability to target and boost specifically the necrosis of monocytic cancer cells. Moreover, the comparison between FLG and a common chemotherapeutic drug, etoposide, confirmed the higher specificity and toxicity of FLG. Since current chemotherapy treatments of leukemia still cause serious problems, these findings open the way to new and safer therapeutic approaches.},
keywords = {Acute, cancer therapy, Chronic, Cultured, graphene, Graphite, Humans, I2CT, Immune System, leukemia, Leukocytes, Mononuclear, Myeloid, Myelomonocytic, myelomonocytic leukemia, Nanomaterials, Particle Size, Surface Properties, Team-Bianco, Tumor Cells},
pubstate = {published},
tppubtype = {article}
}
Nehmar Ramzi, Alsaleh Ghada, Voisin Benjamin, Flacher Vincent, Mariotte Alexandre, Saferding Victoria, Puchner Antonia, Niederreiter Birgit, Vandamme Thierry, Schabbauer Gernot, Kastner Philippe, Chan Susan, Kirstetter Peggy, Holcmann Martin, Mueller Christopher, Sibilia Jean, Bahram Seiamak, Blüml Stephan, Georgel Philippe
Therapeutic Modulation of Plasmacytoid Dendritic Cells in Experimental Arthritis Article de journal
Dans: Arthritis & Rheumatology (Hoboken, N.J.), vol. 69, no. 11, p. 2124–2135, 2017, ISSN: 2326-5205.
Résumé | Liens | BibTeX | Étiquettes: Activation, Adjuvants, Aminoquinolines, Analysis, Animal, Animals, arthritis, Assay, cancer, Cells, cytokine, Cytokines, Dendritic Cells, DEPLETION, Disease Models, drug effects, Enzyme-Linked Immunosorbent Assay, Experimental, Flow Cytometry, Gene Expression Profiling, Genetics, GLYCOPROTEIN, Glycoproteins, Human, Humans, IFN, IKAROS, Ikaros Transcription Factor, imiquimod, Immunologic, Immunology, immunopathology, inflammation, interferon, Interferon Type I, interferons, Knockout, Membrane, Membrane Glycoproteins, METHOD, methods, Mice, MODULATION, mouse, Necrosis, NECROSIS-FACTOR-ALPHA, pathogenesis, Patients, Pharmacology, physiology, plasmacytoid dendritic cells, Protein, Receptor, Reverse Transcriptase Polymerase Chain Reaction, rheumatoid, rheumatoid arthritis, Serum, signaling, Team-Mueller, TLR7, Toll-Like Receptor 7, TOPICAL APPLICATION, Transcription, TRANSCRIPTION FACTOR, transcriptome, transgenic, tumor, Tumor Necrosis Factor, Tumor Necrosis Factor-alpha
@article{nehmar_therapeutic_2017,
title = {Therapeutic Modulation of Plasmacytoid Dendritic Cells in Experimental Arthritis},
author = {Ramzi Nehmar and Ghada Alsaleh and Benjamin Voisin and Vincent Flacher and Alexandre Mariotte and Victoria Saferding and Antonia Puchner and Birgit Niederreiter and Thierry Vandamme and Gernot Schabbauer and Philippe Kastner and Susan Chan and Peggy Kirstetter and Martin Holcmann and Christopher Mueller and Jean Sibilia and Seiamak Bahram and Stephan Blüml and Philippe Georgel},
doi = {10.1002/art.40225},
issn = {2326-5205},
year = {2017},
date = {2017-01-01},
journal = {Arthritis & Rheumatology (Hoboken, N.J.)},
volume = {69},
number = {11},
pages = {2124--2135},
abstract = {OBJECTIVE: The role of plasmacytoid dendritic cells (PDCs) and type I interferons (IFNs) in rheumatoid arthritis (RA) remains a subject of controversy. This study was undertaken to explore the contribution of PDCs and type I IFNs to RA pathogenesis using various animal models of PDC depletion and to monitor the effect of localized PDC recruitment and activation on joint inflammation and bone damage.
METHODS: Mice with K/BxN serum-induced arthritis, collagen-induced arthritis, and human tumor necrosis factor transgene insertion were studied. Symptoms were evaluated by visual scoring, quantification of paw swelling, determination of cytokine levels by enzyme-linked immunosorbent assay, and histologic analysis. Imiquimod-dependent therapeutic effects were monitored by transcriptome analysis (using quantitative reverse transcriptase-polymerase chain reaction) and flow cytometric analysis of the periarticular tissue.
RESULTS: PDC-deficient mice showed exacerbation of inflammatory and arthritis symptoms after arthritogenic serum transfer. In contrast, enhancing PDC recruitment and activation to arthritic joints by topical application of the Toll-like receptor 7 (TLR-7) agonist imiquimod significantly ameliorated arthritis in various mouse models. Imiquimod induced an IFN signature and led to reduced infiltration of inflammatory cells.
CONCLUSION: The therapeutic effects of imiquimod on joint inflammation and bone destruction are dependent on TLR-7 sensing by PDCs and type I IFN signaling. Our findings indicate that local recruitment and activation of PDCs represents an attractive therapeutic opportunity for RA patients.},
keywords = {Activation, Adjuvants, Aminoquinolines, Analysis, Animal, Animals, arthritis, Assay, cancer, Cells, cytokine, Cytokines, Dendritic Cells, DEPLETION, Disease Models, drug effects, Enzyme-Linked Immunosorbent Assay, Experimental, Flow Cytometry, Gene Expression Profiling, Genetics, GLYCOPROTEIN, Glycoproteins, Human, Humans, IFN, IKAROS, Ikaros Transcription Factor, imiquimod, Immunologic, Immunology, immunopathology, inflammation, interferon, Interferon Type I, interferons, Knockout, Membrane, Membrane Glycoproteins, METHOD, methods, Mice, MODULATION, mouse, Necrosis, NECROSIS-FACTOR-ALPHA, pathogenesis, Patients, Pharmacology, physiology, plasmacytoid dendritic cells, Protein, Receptor, Reverse Transcriptase Polymerase Chain Reaction, rheumatoid, rheumatoid arthritis, Serum, signaling, Team-Mueller, TLR7, Toll-Like Receptor 7, TOPICAL APPLICATION, Transcription, TRANSCRIPTION FACTOR, transcriptome, transgenic, tumor, Tumor Necrosis Factor, Tumor Necrosis Factor-alpha},
pubstate = {published},
tppubtype = {article}
}
METHODS: Mice with K/BxN serum-induced arthritis, collagen-induced arthritis, and human tumor necrosis factor transgene insertion were studied. Symptoms were evaluated by visual scoring, quantification of paw swelling, determination of cytokine levels by enzyme-linked immunosorbent assay, and histologic analysis. Imiquimod-dependent therapeutic effects were monitored by transcriptome analysis (using quantitative reverse transcriptase-polymerase chain reaction) and flow cytometric analysis of the periarticular tissue.
RESULTS: PDC-deficient mice showed exacerbation of inflammatory and arthritis symptoms after arthritogenic serum transfer. In contrast, enhancing PDC recruitment and activation to arthritic joints by topical application of the Toll-like receptor 7 (TLR-7) agonist imiquimod significantly ameliorated arthritis in various mouse models. Imiquimod induced an IFN signature and led to reduced infiltration of inflammatory cells.
CONCLUSION: The therapeutic effects of imiquimod on joint inflammation and bone destruction are dependent on TLR-7 sensing by PDCs and type I IFN signaling. Our findings indicate that local recruitment and activation of PDCs represents an attractive therapeutic opportunity for RA patients.
Saliba Hanadi, Heurtault Béatrice, Bouharoun-Tayoun Hasnaa, Flacher Vincent, Frisch Benoît, Fournel Sylvie, Chamat Soulaima
Enhancing tumor specific immune responses by transcutaneous vaccination Article de journal
Dans: Expert Review of Vaccines, vol. 16, no. 11, p. 1079–1094, 2017, ISSN: 1744-8395.
Résumé | Liens | BibTeX | Étiquettes: Administration, Cancer vaccine, Cancer Vaccines, Clinical Trials as Topic, Cutaneous, Dendritic Cells, Humans, liposome, Liposomes, nanoparticle, Nanoparticles, Neoplasms, Skin, skin dendritic cell, Team-Mueller, transcutaneous vaccination, Treatment Outcome, Vaccination
@article{saliba_enhancing_2017,
title = {Enhancing tumor specific immune responses by transcutaneous vaccination},
author = {Hanadi Saliba and Béatrice Heurtault and Hasnaa Bouharoun-Tayoun and Vincent Flacher and Benoît Frisch and Sylvie Fournel and Soulaima Chamat},
doi = {10.1080/14760584.2017.1382357},
issn = {1744-8395},
year = {2017},
date = {2017-01-01},
journal = {Expert Review of Vaccines},
volume = {16},
number = {11},
pages = {1079--1094},
abstract = {INTRODUCTION: Our understanding of the involvement of the immune system in cancer control has increased over recent years. However, the development of cancer vaccines intended to reverse tumor-induced immune tolerance remains slow as most current vaccine candidates exhibit limited clinical efficacy. The skin is particularly rich with multiple subsets of dendritic cells (DCs) that are involved to varying degrees in the induction of robust immune responses. Transcutaneous administration of cancer vaccines may therefore harness the immune potential of these DCs, however, this approach is hampered by the impermeability of the stratum corneum. Innovative vaccine formulations including various nanoparticles, such as liposomes, are therefore needed to properly deliver cancer vaccine components to skin DCs. Areas covered: The recent insights into skin DC subsets and their functional specialization, the potential of nanoparticle-based vaccines in transcutaneous cancer vaccination and, finally, the most relevant clinical trial advances in liposomal and in cutaneous cancer vaccines will be discussed. Expert commentary: To define the optimal conditions for mounting protective skin DC-induced anti-tumor immune responses, investigation of the cellular and molecular interplay that controls tumor progression should be pursued in parallel with clinical development. The resulting knowledge will then be translated into improved cancer vaccines that better target the most appropriate immune players.},
keywords = {Administration, Cancer vaccine, Cancer Vaccines, Clinical Trials as Topic, Cutaneous, Dendritic Cells, Humans, liposome, Liposomes, nanoparticle, Nanoparticles, Neoplasms, Skin, skin dendritic cell, Team-Mueller, transcutaneous vaccination, Treatment Outcome, Vaccination},
pubstate = {published},
tppubtype = {article}
}
2016
Chypre M, Seaman J, Cordeiro O G, Willen L, Knoop K A, Buchanan A, Sainson R C, Williams I R, Yagita H, Schneider P, Mueller C G
Characterization and application of two RANK-specific antibodies with different biological activities Article de journal
Dans: Immunol.Lett., vol. 171, no. 1879-0542 (Electronic), p. 5–14, 2016.
Résumé | Liens | BibTeX | Étiquettes: Activation, Animals, ANTAGONIST, Antibodies, antibody, Antibody Affinity, Apoptosis, Assay, Cell Differentiation, Cell Surface Display Techniques, Cellular, Chemistry, comparison, Dendritic Cells, DERMAL DENDRITIC CELLS, Epithelial Cells, Epithelial microfold cell, Epitopes, Fusion, FUSION PROTEIN, HEK293 Cells, Homeostasis, Human, Humans, immune regulation, Immunization, Immunology, Immunomodulation, immunopathology, In vivo, Inbred C57BL, Intestines, Jurkat Cells, Langerhans cell, Langerhans Cells, Mice, Monoclonal, monoclonal antibody, MONOCLONAL-ANTIBODY, mouse, NF-kappa B, NF-kappaB, pathology, Protein, rank, RANK (TNFRSF11a), Receptor, Receptor Activator of Nuclear Factor-kappa B, Regulation, Secondary, Signal Transduction, signaling, Team-Mueller, therapy
@article{chypre_characterization_2016,
title = {Characterization and application of two RANK-specific antibodies with different biological activities},
author = {M Chypre and J Seaman and O G Cordeiro and L Willen and K A Knoop and A Buchanan and R C Sainson and I R Williams and H Yagita and P Schneider and C G Mueller},
doi = {10.1016/j.imlet.2016.01.003},
year = {2016},
date = {2016-03-01},
journal = {Immunol.Lett.},
volume = {171},
number = {1879-0542 (Electronic)},
pages = {5--14},
abstract = {Antibodies play an important role in therapy and investigative biomedical research. The TNF-family member Receptor Activator of NF-kappaB (RANK) is known for its role in bone homeostasis and is increasingly recognized as a central player in immune regulation and epithelial cell activation. However, the study of RANK biology has been hampered by missing or insufficient characterization of high affinity tools that recognize RANK. Here, we present a careful description and comparison of two antibodies, RANK-02 obtained by phage display (Newa, 2014 [1]) and R12-31 generated by immunization (Kamijo, 2006 [2]). We found that both antibodies recognized mouse RANK with high affinity, while RANK-02 and R12-31 recognized human RANK with high and lower affinities, respectively. Using a cell apoptosis assay based on stimulation of a RANK:Fas fusion protein, and a cellular NF-kappaB signaling assay, we showed that R12-31 was agonist for both species. R12-31 interfered little or not at all with the binding of RANKL to RANK, in contrast to RANK-02 that efficiently prevented this interaction. Depending on the assay and species, RANK-02 was either a weak agonist or a partial antagonist of RANK. Both antibodies recognized human Langerhans cells, previously shown to express RANK, while dermal dendritic cells were poorly labeled. In vivo R12-31 agonist activity was demonstrated by its ability to induce the formation of intestinal villous microfold cells in mice. This characterization of two monoclonal antibodies should now allow better evaluation of their application as therapeutic reagents and investigative tools},
keywords = {Activation, Animals, ANTAGONIST, Antibodies, antibody, Antibody Affinity, Apoptosis, Assay, Cell Differentiation, Cell Surface Display Techniques, Cellular, Chemistry, comparison, Dendritic Cells, DERMAL DENDRITIC CELLS, Epithelial Cells, Epithelial microfold cell, Epitopes, Fusion, FUSION PROTEIN, HEK293 Cells, Homeostasis, Human, Humans, immune regulation, Immunization, Immunology, Immunomodulation, immunopathology, In vivo, Inbred C57BL, Intestines, Jurkat Cells, Langerhans cell, Langerhans Cells, Mice, Monoclonal, monoclonal antibody, MONOCLONAL-ANTIBODY, mouse, NF-kappa B, NF-kappaB, pathology, Protein, rank, RANK (TNFRSF11a), Receptor, Receptor Activator of Nuclear Factor-kappa B, Regulation, Secondary, Signal Transduction, signaling, Team-Mueller, therapy},
pubstate = {published},
tppubtype = {article}
}
Sawaf Matthieu, Dumortier Hélène, Monneaux Fanny
Follicular Helper Ŧ Cells in Systemic Lupus Erythematosus: Why Should They Be Considered as Interesting Therapeutic Targets? Article de journal
Dans: Journal of Immunology Research, vol. 2016, p. 5767106, 2016, ISSN: 2314-7156.
Résumé | Liens | BibTeX | Étiquettes: Adult, Autoantibodies, B-Lymphocytes, Cell Differentiation, Dumortier, Germinal Center, Helper-Inducer, Humans, I2CT, Lupus Erythematosus, Molecular Targeted Therapy, Monneaux, Plasma Cells, Systemic, T-Lymphocytes, Team-Dumortier
@article{sawaf_follicular_2016,
title = {Follicular Helper Ŧ Cells in Systemic Lupus Erythematosus: Why Should They Be Considered as Interesting Therapeutic Targets?},
author = {Matthieu Sawaf and Hélène Dumortier and Fanny Monneaux},
doi = {10.1155/2016/5767106},
issn = {2314-7156},
year = {2016},
date = {2016-01-01},
journal = {Journal of Immunology Research},
volume = {2016},
pages = {5767106},
abstract = {Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by B cell hyperactivity leading to the production of autoantibodies, some of which having a deleterious effect. Reducing autoantibody production thus represents a way of controlling lupus pathogenesis, and a better understanding of the molecular and cellular factors involved in the differentiation of B cells into plasma cells could allow identifying new therapeutic targets. Follicular helper T cells (TFH) represent a distinct subset of CD4(+) T cells specialized in providing help to B cells. They are required for the formation of germinal centers and the generation of long-lived serological memory and, as such, are suspected to play a central role in SLE. Recent advances in the field of TFH biology have allowed the identification of important molecular factors involved in TFH differentiation, regulation, and function. Interestingly, some of these TFH-related molecules have been described to be dysregulated in lupus patients. In the present review, we give an overview of the aberrant expression and/or function of such key players in lupus, and we highlight their potential as therapeutic targets.},
keywords = {Adult, Autoantibodies, B-Lymphocytes, Cell Differentiation, Dumortier, Germinal Center, Helper-Inducer, Humans, I2CT, Lupus Erythematosus, Molecular Targeted Therapy, Monneaux, Plasma Cells, Systemic, T-Lymphocytes, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
Dietrich Damien, Martin Praxedis, Flacher Vincent, Sun Yu, Jarrossay David, Brembilla Nicolo, Mueller Christopher, Arnett Heather A, Palmer Gaby, Towne Jennifer, Gabay Cem
Interleukin-36 potently stimulates human M2 macrophages, Langerhans cells and keratinocytes to produce pro-inflammatory cytokines Article de journal
Dans: Cytokine, vol. 84, p. 88–98, 2016, ISSN: 1096-0023.
Résumé | Liens | BibTeX | Étiquettes: agonists, ANTAGONIST, BLOOD, Cells, Cellular, Chemistry, Cultured, cytokine, CYTOKINE PRODUCTION, Cytokines, Dendritic Cells, DERMATOLOGY, Expression, Human, Humans, IL-1, IL-1R1, IL-1ra, IL-36, IL-36R, Immunoassay, Immunology, immunopathology, inflammation, Interleukin, Interleukin-1 Receptor Accessory Protein, Interleukin-1 Type I, KERATINOCYTES, Langerhans Cells, Macrophage, Macrophages, messenger, Molecular Biology, Monocytes, mRNA, Myeloid Cells, pathology, Phenotype, PRODUCTION, PROINFLAMMATORY CYTOKINES, Receptor, receptor antagonist, Receptors, RNA, signaling, Skin, target, Team-Mueller, TONSIL
@article{dietrich_interleukin-36_2016,
title = {Interleukin-36 potently stimulates human M2 macrophages, Langerhans cells and keratinocytes to produce pro-inflammatory cytokines},
author = {Damien Dietrich and Praxedis Martin and Vincent Flacher and Yu Sun and David Jarrossay and Nicolo Brembilla and Christopher Mueller and Heather A Arnett and Gaby Palmer and Jennifer Towne and Cem Gabay},
doi = {10.1016/j.cyto.2016.05.012},
issn = {1096-0023},
year = {2016},
date = {2016-01-01},
journal = {Cytokine},
volume = {84},
pages = {88--98},
abstract = {Interleukin (IL)-36 cytokines belong to the IL-1 family and include three agonists, IL-36 α, β and γ and one inhibitor, IL-36 receptor antagonist (IL-36Ra). IL-36 and IL-1 (α and β) activate similar intracellular pathways via their related heterodimeric receptors, IL-36R/IL-1RAcP and IL-1R1/IL-1RAcP, respectively. However, excessive IL-36 versus IL-1 signaling induces different phenotypes in humans, which may be related to differential expression of their respective receptors. We examined the expression of IL-36R, IL-1R1 and IL-1RAcP mRNA in human peripheral blood, tonsil and skin immune cells by RT-qPCR. Monocyte-derived dendritic cells (MDDC), M0, M1 or M2-polarized macrophages, primary keratinocytes, dermal macrophages and Langerhans cells (LC) were stimulated with IL-1β or IL-36β. Cytokine production was assessed by RT-qPCR and immunoassays. The highest levels of IL-36R mRNA were found in skin-derived keratinocytes, LC, dermal macrophages and dermal CD1a(+) DC. In the blood and in tonsils, IL-36R mRNA was predominantly found in myeloid cells. By contrast, IL-1R1 mRNA was detected in almost all cell types with higher levels in tonsil and skin compared to peripheral blood immune cells. IL-36β was as potent as IL-1β in stimulating M2 macrophages, keratinocytes and LC, less potent than IL-1β in stimulating M0 macrophages and MDDC, and exerted no effects in M1 and dermal macrophages. Levels of IL-1Ra diminished the ability of M2 macrophages to respond to IL-1. Taken together, these data are consistent with the association of excessive IL-36 signaling with an inflammatory skin phenotype and identify human LC and M2 macrophages as new IL-36 target cells.},
keywords = {agonists, ANTAGONIST, BLOOD, Cells, Cellular, Chemistry, Cultured, cytokine, CYTOKINE PRODUCTION, Cytokines, Dendritic Cells, DERMATOLOGY, Expression, Human, Humans, IL-1, IL-1R1, IL-1ra, IL-36, IL-36R, Immunoassay, Immunology, immunopathology, inflammation, Interleukin, Interleukin-1 Receptor Accessory Protein, Interleukin-1 Type I, KERATINOCYTES, Langerhans Cells, Macrophage, Macrophages, messenger, Molecular Biology, Monocytes, mRNA, Myeloid Cells, pathology, Phenotype, PRODUCTION, PROINFLAMMATORY CYTOKINES, Receptor, receptor antagonist, Receptors, RNA, signaling, Skin, target, Team-Mueller, TONSIL},
pubstate = {published},
tppubtype = {article}
}
2015
Flacher Vincent, Neuberg Patrick, Point Floriane, Daubeuf François, Muller Quentin, Sigwalt David, Fauny Jean-Daniel, Remy Jean-Serge, Frossard Nelly, Wagner Alain, Mueller Christopher G, Schaeffer Evelyne
Mannoside Glycolipid Conjugates Display Anti-inflammatory Activity by Inhibition of Toll-like Receptor-4 Mediated Cell Activation Article de journal
Dans: ACS chemical biology, vol. 10, no. 12, p. 2697–2705, 2015, ISSN: 1554-8937.
Résumé | Liens | BibTeX | Étiquettes: Activation, Animals, Anti-Inflammatory Agents, Carbohydrate Sequence, CD14, Cell Membrane, Cells, Chemistry, Cultured, cytokine, Dendritic Cells, development, disease, Glycolipids, Human, Humans, immunopathology, Inbred BALB C, inflammation, inhibition, lipid, lipopolysaccharide, Lipopolysaccharides, LPS, LUNG, Mannosides, Maturation, Membrane, Mice, monocyte, Monocytes, mouse, neutrophils, NF-kappaB, Pneumonia, Protein-Serine-Threonine Kinases, Receptor, secretion, signaling, Structure-Activity Relationship, Tail, Team-Mueller, TLR4, Toll-Like Receptor 4
@article{flacher_mannoside_2015b,
title = {Mannoside Glycolipid Conjugates Display Anti-inflammatory Activity by Inhibition of Toll-like Receptor-4 Mediated Cell Activation},
author = {Vincent Flacher and Patrick Neuberg and Floriane Point and François Daubeuf and Quentin Muller and David Sigwalt and Jean-Daniel Fauny and Jean-Serge Remy and Nelly Frossard and Alain Wagner and Christopher G Mueller and Evelyne Schaeffer},
doi = {10.1021/acschembio.5b00552},
issn = {1554-8937},
year = {2015},
date = {2015-12-01},
journal = {ACS chemical biology},
volume = {10},
number = {12},
pages = {2697--2705},
abstract = {Inhibition of excessive Toll-like receptor 4 (TLR4) signaling is a therapeutic approach pursued for many inflammatory diseases. We report that Mannoside Glycolipid Conjugates (MGCs) selectively blocked TLR4-mediated activation of human monocytes and monocyte-derived dendritic cells (DCs) by lipopolysaccharide (LPS). They potently suppressed pro-inflammatory cytokine secretion and maturation of DCs exposed to LPS, leading to impaired T cell stimulation. MGCs did not interfere with LPS and could act in a delayed manner, hours after LPS stimulation. Their inhibitory action required both the sugar heads and the lipid chain, although the nature of the sugar and the structure of the lipid tail could be modified. They blocked early signaling events at the cell membrane, enhanced internalization of CD14 receptors, and prevented colocalization of CD14 and TLR4, thereby abolishing NF-κB nuclear translocation. When the best lead conjugate was tested in a mouse model of LPS-induced acute lung inflammation, it displayed an anti-inflammatory action by suppressing the recruitment of neutrophils. Thus, MGCs could serve as promising leads for the development of selective TLR4 antagonistic agents for inflammatory diseases.},
keywords = {Activation, Animals, Anti-Inflammatory Agents, Carbohydrate Sequence, CD14, Cell Membrane, Cells, Chemistry, Cultured, cytokine, Dendritic Cells, development, disease, Glycolipids, Human, Humans, immunopathology, Inbred BALB C, inflammation, inhibition, lipid, lipopolysaccharide, Lipopolysaccharides, LPS, LUNG, Mannosides, Maturation, Membrane, Mice, monocyte, Monocytes, mouse, neutrophils, NF-kappaB, Pneumonia, Protein-Serine-Threonine Kinases, Receptor, secretion, signaling, Structure-Activity Relationship, Tail, Team-Mueller, TLR4, Toll-Like Receptor 4},
pubstate = {published},
tppubtype = {article}
}
Mairhofer David G, Ortner Daniela, Tripp Christoph H, Schaffenrath Sandra, Fleming Viktor, Heger Lukas, Komenda Kerstin, Reider Daniela, Dudziak Diana, Chen Suzie, Becker Jürgen C, Flacher Vincent, Stoitzner Patrizia
Impaired gp100-Specific CD8(+) Ŧ-Cell Responses in the Presence of Myeloid-Derived Suppressor Cells in a Spontaneous Mouse Melanoma Model Article de journal
Dans: The Journal of Investigative Dermatology, vol. 135, no. 11, p. 2785–2793, 2015, ISSN: 1523-1747.
Résumé | Liens | BibTeX | Étiquettes: Analysis of Variance, Animal, Animals, Antigen, cancer, CARCINOGENESIS, CD8-Positive T-Lymphocytes, Cell Proliferation, Cultured, DERMATOLOGY, development, disease, Disease Models, Experimental, GLYCOPROTEIN, gp100 Melanoma Antigen, Growth, Human, Humans, Immunity, Immunologic, IN VITRO, Inbred C57BL, iNOS, Leukocytes, LYMPH, LYMPH NODE, Lymph Nodes, Lymphocyte Activation, MELANOCYTES, Melanoma, Mice, mouse, murine, NITRIC OXIDE, nitric oxide synthase, Phenotype, Proliferation, Random Allocation, Receptor, Regulatory, RESPONSES, Skin, SUBSETS, Suppressor Factors, T CELLS, T-CELLS, T-Lymphocytes, Team-Mueller, Transforming Growth Factor beta, transgenic, tumor, Tumor Cells, tumor immunity
@article{mairhofer_impaired_2015,
title = {Impaired gp100-Specific CD8(+) Ŧ-Cell Responses in the Presence of Myeloid-Derived Suppressor Cells in a Spontaneous Mouse Melanoma Model},
author = {David G Mairhofer and Daniela Ortner and Christoph H Tripp and Sandra Schaffenrath and Viktor Fleming and Lukas Heger and Kerstin Komenda and Daniela Reider and Diana Dudziak and Suzie Chen and Jürgen C Becker and Vincent Flacher and Patrizia Stoitzner},
doi = {10.1038/jid.2015.241},
issn = {1523-1747},
year = {2015},
date = {2015-11-01},
journal = {The Journal of Investigative Dermatology},
volume = {135},
number = {11},
pages = {2785--2793},
abstract = {Murine tumor models that closely reflect human diseases are important tools to investigate carcinogenesis and tumor immunity. The transgenic (tg) mouse strain tg(Grm1)EPv develops spontaneous melanoma due to ectopic overexpression of the metabotropic glutamate receptor 1 (Grm1) in melanocytes. In the present study, we characterized the immune status and functional properties of immune cells in tumor-bearing mice. Melanoma development was accompanied by a reduction in the percentages of CD4(+) T cells including regulatory T cells (Tregs) in CD45(+) leukocytes present in tumor tissue and draining lymph nodes (LNs). In contrast, the percentages of CD8(+) T cells were unchanged, and these cells showed an activated phenotype in tumor mice. Endogenous melanoma-associated antigen glycoprotein 100 (gp100)-specific CD8(+) T cells were not deleted during tumor development, as revealed by pentamer staining in the skin and draining LNs. They, however, were unresponsive to ex vivo gp100-peptide stimulation in late-stage tumor mice. Interestingly, immunosuppressive myeloid-derived suppressor cells (MDSCs) were recruited to tumor tissue with a preferential accumulation of granulocytic MDSC (grMDSCs) over monocytic MDSC (moMDSCs). Both subsets produced Arginase-1, inducible nitric oxide synthase (iNOS), and transforming growth factor-β and suppressed T-cell proliferation in vitro. In this work, we describe the immune status of a spontaneous melanoma mouse model that provides an interesting tool to develop future immunotherapeutical strategies.},
keywords = {Analysis of Variance, Animal, Animals, Antigen, cancer, CARCINOGENESIS, CD8-Positive T-Lymphocytes, Cell Proliferation, Cultured, DERMATOLOGY, development, disease, Disease Models, Experimental, GLYCOPROTEIN, gp100 Melanoma Antigen, Growth, Human, Humans, Immunity, Immunologic, IN VITRO, Inbred C57BL, iNOS, Leukocytes, LYMPH, LYMPH NODE, Lymph Nodes, Lymphocyte Activation, MELANOCYTES, Melanoma, Mice, mouse, murine, NITRIC OXIDE, nitric oxide synthase, Phenotype, Proliferation, Random Allocation, Receptor, Regulatory, RESPONSES, Skin, SUBSETS, Suppressor Factors, T CELLS, T-CELLS, T-Lymphocytes, Team-Mueller, Transforming Growth Factor beta, transgenic, tumor, Tumor Cells, tumor immunity},
pubstate = {published},
tppubtype = {article}
}
Schaeffer Evelyne, Flacher Vincent, Papageorgiou Vasiliki, Decossas Marion, Fauny Jean-Daniel, Krämer Melanie, Mueller Christopher G
Dermal CD14(+) Dendritic Cell and Macrophage Infection by Dengue Virus Is Stimulated by Interleukin-4 Article de journal
Dans: The Journal of Investigative Dermatology, vol. 135, no. 7, p. 1743–1751, 2015, ISSN: 1523-1747.
Résumé | Liens | BibTeX | Étiquettes: Abdominal Wall, Activation, Adhesion, adhesion molecules, Antigen-Presenting Cells, arbovirus, C-Type, Cell Adhesion, Cell Adhesion Molecules, Cell Surface, Cells, Chemistry, Confocal, Cultured, cytokine, Cytokines, cytology, Dendritic Cells, Dengue, Dengue virus, DERMAL DENDRITIC CELLS, Dermatitis, DERMIS, development, disease, Enzyme-Linked Immunosorbent Assay, Epidermal Cells, Epidermis, Human, Humans, ICAM-3, IL-4, Immunology, immunopathology, infection, Interleukin-4, Langerhans Cells, LECTIN, Lectins, Lymphocyte Activation, Macrophage, Macrophages, metabolism, Microscopy, pathogenicity, physiopathology, Receptor, Receptors, Scabies, Sensitivity and Specificity, Skin, Skin Diseases, SUBSETS, T CELL ACTIVATION, target, Team-Mueller, TNF ALPHA, Viral, viral Infection, Viral Load, virology, virus
@article{schaeffer_dermal_2015b,
title = {Dermal CD14(+) Dendritic Cell and Macrophage Infection by Dengue Virus Is Stimulated by Interleukin-4},
author = {Evelyne Schaeffer and Vincent Flacher and Vasiliki Papageorgiou and Marion Decossas and Jean-Daniel Fauny and Melanie Krämer and Christopher G Mueller},
doi = {10.1038/jid.2014.525},
issn = {1523-1747},
year = {2015},
date = {2015-07-01},
journal = {The Journal of Investigative Dermatology},
volume = {135},
number = {7},
pages = {1743--1751},
abstract = {Dengue virus (DENV) is responsible for the most prevalent arthropod-borne viral infection in humans. Events decisive for disease development occur in the skin after virus inoculation by the mosquito. Yet, the role of human dermis-resident immune cells in dengue infection and disease remains elusive. Here we investigated how dermal dendritic cells (dDCs) and macrophages (dMs) react to DENV and impact on immunopathology. We show that both CD1c(+) and CD14(+) dDC subsets were infected, but viral load greatly increased in CD14(+) dDCs upon IL-4 stimulation, which correlated with upregulation of virus-binding lectins Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Nonintegrin (DC-SIGN/CD209) and mannose receptor (CD206). IL-4 also enhanced T-cell activation by dDCs, which was further increased upon dengue infection. dMs purified from digested dermis were initially poorly infected but actively replicated the virus and produced TNF-α upon lectin upregulation in response to IL-4. DC-SIGN(+) cells are abundant in inflammatory skin with scabies infection or Th2-type dermatitis, suggesting that skin reactions to mosquito bites heighten the risk of infection and subsequent immunopathology. Our data identify dDCs and dMs as primary arbovirus target cells in humans and suggest that dDCs initiate a potent virus-directed T-cell response, whereas dMs fuel the inflammatory cascade characteristic of dengue fever.},
keywords = {Abdominal Wall, Activation, Adhesion, adhesion molecules, Antigen-Presenting Cells, arbovirus, C-Type, Cell Adhesion, Cell Adhesion Molecules, Cell Surface, Cells, Chemistry, Confocal, Cultured, cytokine, Cytokines, cytology, Dendritic Cells, Dengue, Dengue virus, DERMAL DENDRITIC CELLS, Dermatitis, DERMIS, development, disease, Enzyme-Linked Immunosorbent Assay, Epidermal Cells, Epidermis, Human, Humans, ICAM-3, IL-4, Immunology, immunopathology, infection, Interleukin-4, Langerhans Cells, LECTIN, Lectins, Lymphocyte Activation, Macrophage, Macrophages, metabolism, Microscopy, pathogenicity, physiopathology, Receptor, Receptors, Scabies, Sensitivity and Specificity, Skin, Skin Diseases, SUBSETS, T CELL ACTIVATION, target, Team-Mueller, TNF ALPHA, Viral, viral Infection, Viral Load, virology, virus},
pubstate = {published},
tppubtype = {article}
}
Paro Simona, Imler Jean-Luc, Meignin Carine
Sensing viral RNAs by Dicer/RIG-I like ATPases across species Article de journal
Dans: Current Opinion in Immunology, vol. 32, p. 106–113, 2015, ISSN: 1879-0372.
Résumé | Liens | BibTeX | Étiquettes: Adenosine Triphosphatases, Animals, DEAD-box RNA Helicases, Humans, imler, M3i, meignin, Protein Binding, Protein Interaction Domains and Motifs, Ribonuclease III, RNA, Viral, Virus Diseases, viruses
@article{paro_sensing_2015,
title = {Sensing viral RNAs by Dicer/RIG-I like ATPases across species},
author = {Simona Paro and Jean-Luc Imler and Carine Meignin},
url = {http://linkinghub.elsevier.com/retrieve/pii/S0952791515000102},
doi = {10.1016/j.coi.2015.01.009},
issn = {1879-0372},
year = {2015},
date = {2015-02-01},
journal = {Current Opinion in Immunology},
volume = {32},
pages = {106--113},
abstract = {Induction of antiviral immunity in vertebrates and invertebrates relies on members of the RIG-I-like receptor and Dicer families, respectively. Although these proteins have different size and domain composition, members of both families share a conserved DECH-box helicase domain. This helicase, also known as a duplex RNA activated ATPase, or DRA domain, plays an important role in viral RNA sensing. Crystallographic and electron microscopy studies of the RIG-I and Dicer DRA domains indicate a common structure and that similar conformational changes are induced by dsRNA binding. Genetic and biochemical studies on the function and regulation of DRAs reveal similarities, but also some differences, between viral RNA sensing mechanisms in nematodes, flies and mammals.},
keywords = {Adenosine Triphosphatases, Animals, DEAD-box RNA Helicases, Humans, imler, M3i, meignin, Protein Binding, Protein Interaction Domains and Motifs, Ribonuclease III, RNA, Viral, Virus Diseases, viruses},
pubstate = {published},
tppubtype = {article}
}
Schaeffer Evelyne, Flacher Vincent, Papageorgiou Vasiliki, Decossas Marion, Fauny Jean-Daniel, Krämer Melanie, Mueller Christopher G
Dermal CD14(+) Dendritic Cell and Macrophage Infection by Dengue Virus Is Stimulated by Interleukin-4 Article de journal
Dans: The Journal of Investigative Dermatology, vol. 135, no. 7, p. 1743–1751, 2015, ISSN: 1523-1747.
Résumé | Liens | BibTeX | Étiquettes: Abdominal Wall, Antigen-Presenting Cells, C-Type, Cell Adhesion Molecules, Cell Surface, Cells, Confocal, Cultured, Cytokines, Dengue, Dengue virus, Enzyme-Linked Immunosorbent Assay, Epidermis, Humans, I2CT, Imagerie, Interleukin-4, Langerhans Cells, Lectins, Lymphocyte Activation, Macrophages, Microscopy, Receptors, Sensitivity and Specificity, Skin Diseases, Team-Mueller, Viral
@article{schaeffer_dermal_2015,
title = {Dermal CD14(+) Dendritic Cell and Macrophage Infection by Dengue Virus Is Stimulated by Interleukin-4},
author = {Evelyne Schaeffer and Vincent Flacher and Vasiliki Papageorgiou and Marion Decossas and Jean-Daniel Fauny and Melanie Krämer and Christopher G Mueller},
doi = {10.1038/jid.2014.525},
issn = {1523-1747},
year = {2015},
date = {2015-01-01},
journal = {The Journal of Investigative Dermatology},
volume = {135},
number = {7},
pages = {1743--1751},
abstract = {Dengue virus (DENV) is responsible for the most prevalent arthropod-borne viral infection in humans. Events decisive for disease development occur in the skin after virus inoculation by the mosquito. Yet, the role of human dermis-resident immune cells in dengue infection and disease remains elusive. Here we investigated how dermal dendritic cells (dDCs) and macrophages (dMs) react to DENV and impact on immunopathology. We show that both CD1c(+) and CD14(+) dDC subsets were infected, but viral load greatly increased in CD14(+) dDCs upon IL-4 stimulation, which correlated with upregulation of virus-binding lectins Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Nonintegrin (DC-SIGN/CD209) and mannose receptor (CD206). IL-4 also enhanced T-cell activation by dDCs, which was further increased upon dengue infection. dMs purified from digested dermis were initially poorly infected but actively replicated the virus and produced TNF-α upon lectin upregulation in response to IL-4. DC-SIGN(+) cells are abundant in inflammatory skin with scabies infection or Th2-type dermatitis, suggesting that skin reactions to mosquito bites heighten the risk of infection and subsequent immunopathology. Our data identify dDCs and dMs as primary arbovirus target cells in humans and suggest that dDCs initiate a potent virus-directed T-cell response, whereas dMs fuel the inflammatory cascade characteristic of dengue fever.},
keywords = {Abdominal Wall, Antigen-Presenting Cells, C-Type, Cell Adhesion Molecules, Cell Surface, Cells, Confocal, Cultured, Cytokines, Dengue, Dengue virus, Enzyme-Linked Immunosorbent Assay, Epidermis, Humans, I2CT, Imagerie, Interleukin-4, Langerhans Cells, Lectins, Lymphocyte Activation, Macrophages, Microscopy, Receptors, Sensitivity and Specificity, Skin Diseases, Team-Mueller, Viral},
pubstate = {published},
tppubtype = {article}
}
Jacquemin Clément, Schmitt Nathalie, Contin-Bordes Cécile, Liu Yang, Narayanan Priya, Seneschal Julien, Maurouard Typhanie, Dougall David, Davizon Emily Spence, Dumortier Hélène, Douchet Isabelle, Raffray Loïc, Richez Christophe, Lazaro Estibaliz, Duffau Pierre, Truchetet Marie-Elise, Khoryati Liliane, Mercié Patrick, Couzi Lionel, Merville Pierre, Schaeverbeke Thierry, Viallard Jean-François, Pellegrin Jean-Luc, Moreau Jean-François, Muller Sylviane, Zurawski Sandy, Coffman Robert L, Pascual Virginia, Ueno Hideki, Blanco Patrick
OX40 Ligand Contributes to Human Lupus Pathogenesis by Promoting Ŧ Follicular Helper Response Article de journal
Dans: Immunity, vol. 42, no. 6, p. 1159–1170, 2015, ISSN: 1097-4180.
Résumé | Liens | BibTeX | Étiquettes: Adolescent, Adult, Aged, Antigen Presentation, B-Lymphocytes, Cell Differentiation, Cells, Cultured, Cytokines, Disease Progression, Dumortier, Female, Helper-Inducer, Humans, I2CT, Immunologic Memory, Inducible T-Cell Co-Stimulator Protein, Lupus Erythematosus, Lymphocyte Activation, Male, Middle Aged, Molecular Targeted Therapy, Myeloid Cells, OX40, OX40 Ligand, Receptors, RNA, Signal Transduction, Systemic, T-Lymphocytes, Team-Dumortier, Toll-Like Receptor 7, Young Adult
@article{jacquemin_ox40_2015,
title = {OX40 Ligand Contributes to Human Lupus Pathogenesis by Promoting Ŧ Follicular Helper Response},
author = {Clément Jacquemin and Nathalie Schmitt and Cécile Contin-Bordes and Yang Liu and Priya Narayanan and Julien Seneschal and Typhanie Maurouard and David Dougall and Emily Spence Davizon and Hélène Dumortier and Isabelle Douchet and Loïc Raffray and Christophe Richez and Estibaliz Lazaro and Pierre Duffau and Marie-Elise Truchetet and Liliane Khoryati and Patrick Mercié and Lionel Couzi and Pierre Merville and Thierry Schaeverbeke and Jean-François Viallard and Jean-Luc Pellegrin and Jean-François Moreau and Sylviane Muller and Sandy Zurawski and Robert L Coffman and Virginia Pascual and Hideki Ueno and Patrick Blanco},
doi = {10.1016/j.immuni.2015.05.012},
issn = {1097-4180},
year = {2015},
date = {2015-01-01},
journal = {Immunity},
volume = {42},
number = {6},
pages = {1159--1170},
abstract = {Increased activity of T follicular helper (Tfh) cells plays a major pathogenic role in systemic lupus erythematosus (SLE). However, the mechanisms that cause aberrant Tfh cell responses in SLE remain elusive. Here we showed the OX40 ligand (OX40L)-OX40 axis contributes to the aberrant Tfh response in SLE. OX40L was expressed by myeloid antigen-presenting cells (APCs), but not B cells, in blood and in inflamed tissues in adult and pediatric SLE patients. The frequency of circulating OX40L-expressing myeloid APCs positively correlated with disease activity and the frequency of ICOS(+) blood Tfh cells in SLE. OX40 signals promoted naive and memory CD4(+) T cells to express multiple Tfh cell molecules and were sufficient to induce them to become functional B cell helpers. Immune complexes containing RNA induced OX40L expression on myeloid APCs via TLR7 activation. Our study provides a rationale to target the OX40L-OX40 axis as a therapeutic modality for SLE.},
keywords = {Adolescent, Adult, Aged, Antigen Presentation, B-Lymphocytes, Cell Differentiation, Cells, Cultured, Cytokines, Disease Progression, Dumortier, Female, Helper-Inducer, Humans, I2CT, Immunologic Memory, Inducible T-Cell Co-Stimulator Protein, Lupus Erythematosus, Lymphocyte Activation, Male, Middle Aged, Molecular Targeted Therapy, Myeloid Cells, OX40, OX40 Ligand, Receptors, RNA, Signal Transduction, Systemic, T-Lymphocytes, Team-Dumortier, Toll-Like Receptor 7, Young Adult},
pubstate = {published},
tppubtype = {article}
}
Karttunen Sarah, Duffield Michael, Scrimgeour Nathan R, Squires Lauren, Lim Wai Li, Dallas Mark L, Scragg Jason L, Chicher Johana, Dave Keyur A, Whitelaw Murray L, Peers Chris, Gorman Jeffrey J, Gleadle Jonathan M, Rychkov Grigori Y, Peet Daniel J
Oxygen-dependent hydroxylation by FIH regulates the TRPV3 ion channel. Article de journal
Dans: Journal of cell science, vol. 128, no. 2, p. 225–231, 2015, ISSN: 1477-9137 0021-9533, (Place: England).
Résumé | Liens | BibTeX | Étiquettes: alpha Subunit/genetics/*metabolism, Amino Acid Sequence, Ankyrin Repeat/genetics, Cell Hypoxia/*genetics, FIH, HEK293 Cells, Humans, Hydroxylation, Hydroxylation/genetics, Hypoxia, Hypoxia-Inducible Factor 1, Mixed Function Oxygenases/antagonists & inhibitors/genetics/*metabolism, Mutation, Oxygen/metabolism, PPSE, Protein Binding, Repressor Proteins/antagonists & inhibitors/genetics/*metabolism, TRPV Cation Channels/genetics/*metabolism, TRPV3
@article{karttunen_oxygen-dependent_2015,
title = {Oxygen-dependent hydroxylation by FIH regulates the TRPV3 ion channel.},
author = {Sarah Karttunen and Michael Duffield and Nathan R Scrimgeour and Lauren Squires and Wai Li Lim and Mark L Dallas and Jason L Scragg and Johana Chicher and Keyur A Dave and Murray L Whitelaw and Chris Peers and Jeffrey J Gorman and Jonathan M Gleadle and Grigori Y Rychkov and Daniel J Peet},
doi = {10.1242/jcs.158451},
issn = {1477-9137 0021-9533},
year = {2015},
date = {2015-01-01},
journal = {Journal of cell science},
volume = {128},
number = {2},
pages = {225--231},
abstract = {Factor inhibiting HIF (FIH, also known as HIF1AN) is an oxygen-dependent asparaginyl hydroxylase that regulates the hypoxia-inducible factors (HIFs). Several proteins containing ankyrin repeat domains (ARDs) have been characterised as substrates of FIH, although there is little evidence for a functional consequence of hydroxylation on these substrates. This study demonstrates that the transient receptor potential vanilloid 3 (TRPV3) channel is hydroxylated by FIH on asparagine 242 within the cytoplasmic ARD. Hypoxia, FIH inhibitors and mutation of asparagine 242 all potentiated TRPV3-mediated current, without altering TRPV3 protein levels, indicating that oxygen-dependent hydroxylation inhibits TRPV3 activity. This novel mechanism of channel regulation by oxygen-dependent asparaginyl hydroxylation is likely to extend to other ion channels.},
note = {Place: England},
keywords = {alpha Subunit/genetics/*metabolism, Amino Acid Sequence, Ankyrin Repeat/genetics, Cell Hypoxia/*genetics, FIH, HEK293 Cells, Humans, Hydroxylation, Hydroxylation/genetics, Hypoxia, Hypoxia-Inducible Factor 1, Mixed Function Oxygenases/antagonists & inhibitors/genetics/*metabolism, Mutation, Oxygen/metabolism, PPSE, Protein Binding, Repressor Proteins/antagonists & inhibitors/genetics/*metabolism, TRPV Cation Channels/genetics/*metabolism, TRPV3},
pubstate = {published},
tppubtype = {article}
}
2014
Tartey Sarang, Matsushita Kazufumi, Vandenbon Alexis, Ori Daisuke, Imamura Tomoko, Mino Takashi, Standley Daron M, Hoffmann Jules A, Reichhart Jean-Marc, Akira Shizuo, Takeuchi Osamu
Akirin2 is critical for inducing inflammatory genes by bridging IκB-ζ and the SWI/SNF complex Article de journal
Dans: EMBO J., vol. 33, no. 20, p. 2332–2348, 2014, ISSN: 1460-2075.
Résumé | Liens | BibTeX | Étiquettes: Adaptor Proteins, Animals, Cell Nucleus, Chromatin Assembly and Disassembly, chromatin remodeling, Chromosomal Proteins, cytokine, Cytokines, Female, Gene Expression Regulation, gene regulation, Genetic, hoffmann, Humans, Immunity, Innate, innate immunity, Knockout, Listeria monocytogenes, M3i, Macrophages, Male, Mice, Multiprotein Complexes, Non-Histone, Nuclear Proteins, Promoter Regions, Protein Binding, reichhart, Repressor Proteins, Sequence Deletion, Signal Transducing, Transcriptional Activation
@article{tartey_akirin2_2014,
title = {Akirin2 is critical for inducing inflammatory genes by bridging IκB-ζ and the SWI/SNF complex},
author = {Sarang Tartey and Kazufumi Matsushita and Alexis Vandenbon and Daisuke Ori and Tomoko Imamura and Takashi Mino and Daron M Standley and Jules A Hoffmann and Jean-Marc Reichhart and Shizuo Akira and Osamu Takeuchi},
doi = {10.15252/embj.201488447},
issn = {1460-2075},
year = {2014},
date = {2014-10-01},
journal = {EMBO J.},
volume = {33},
number = {20},
pages = {2332--2348},
abstract = {Transcription of inflammatory genes in innate immune cells is coordinately regulated by transcription factors, including NF-κB, and chromatin modifiers. However, it remains unclear how microbial sensing initiates chromatin remodeling. Here, we show that Akirin2, an evolutionarily conserved nuclear protein, bridges NF-κB and the chromatin remodeling SWI/SNF complex by interacting with BRG1-Associated Factor 60 (BAF60) proteins as well as IκB-ζ, which forms a complex with the NF-κB p50 subunit. These interactions are essential for Toll-like receptor-, RIG-I-, and Listeria-mediated expression of proinflammatory genes including Il6 and Il12b in macrophages. Consistently, effective clearance of Listeria infection required Akirin2. Furthermore, Akirin2 and IκB-ζ recruitment to the Il6 promoter depend upon the presence of IκB-ζ and Akirin2, respectively, for regulation of chromatin remodeling. BAF60 proteins were also essential for the induction of Il6 in response to LPS stimulation. Collectively, the IκB-ζ-Akirin2-BAF60 complex physically links the NF-κB and SWI/SNF complexes in innate immune cell activation. By recruiting SWI/SNF chromatin remodellers to IκB-ζ, transcriptional coactivator for NF-κB, the conserved nuclear protein Akirin2 stimulates pro-inflammatory gene promoters in mouse macrophages during innate immune responses to viral or bacterial infection.},
keywords = {Adaptor Proteins, Animals, Cell Nucleus, Chromatin Assembly and Disassembly, chromatin remodeling, Chromosomal Proteins, cytokine, Cytokines, Female, Gene Expression Regulation, gene regulation, Genetic, hoffmann, Humans, Immunity, Innate, innate immunity, Knockout, Listeria monocytogenes, M3i, Macrophages, Male, Mice, Multiprotein Complexes, Non-Histone, Nuclear Proteins, Promoter Regions, Protein Binding, reichhart, Repressor Proteins, Sequence Deletion, Signal Transducing, Transcriptional Activation},
pubstate = {published},
tppubtype = {article}
}
Imler Jean-Luc
Overview of Drosophila immunity: a historical perspective Article de journal
Dans: Developmental and Comparative Immunology, vol. 42, no. 1, p. 3–15, 2014, ISSN: 1879-0089.
Résumé | Liens | BibTeX | Étiquettes: Allergy and Immunology, Animal, Animals, Antimicrobial Cationic Peptides, Antimicrobial peptides, history, Humans, IMD pathway, imler, Immunity, Innate, innate immunity, M3i, Models, Pattern recognition receptors, Signal Transduction, Toll-Like Receptors
@article{imler_overview_2014,
title = {Overview of Drosophila immunity: a historical perspective},
author = {Jean-Luc Imler},
doi = {10.1016/j.dci.2013.08.018},
issn = {1879-0089},
year = {2014},
date = {2014-01-01},
journal = {Developmental and Comparative Immunology},
volume = {42},
number = {1},
pages = {3--15},
abstract = {The functional analysis of genes from the model organism Drosophila melanogaster has provided invaluable information for many cellular and developmental or physiological processes, including immunity. The best-understood aspect of Drosophila immunity is the inducible humoral response, first recognized in 1972. This pioneering work led to a remarkable series of findings over the next 30 years, ranging from the identification and characterization of the antimicrobial peptides produced, to the deciphering of the signalling pathways activating the genes that encode them and, ultimately, to the discovery of the receptors sensing infection. These studies on an insect model coincided with a revival of the field of innate immunity, and had an unanticipated impact on the biomedical field.},
keywords = {Allergy and Immunology, Animal, Animals, Antimicrobial Cationic Peptides, Antimicrobial peptides, history, Humans, IMD pathway, imler, Immunity, Innate, innate immunity, M3i, Models, Pattern recognition receptors, Signal Transduction, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
Lamanna Giuseppe, Grillaud Maxime, Macri Christophe, Chaloin Olivier, Muller Sylviane, Bianco Alberto
Adamantane-based dendrons for trimerization of the therapeutic P140 peptide Article de journal
Dans: Biomaterials, vol. 35, no. 26, p. 7553–7561, 2014, ISSN: 1878-5905.
Résumé | Liens | BibTeX | Étiquettes: Adamantane, Animals, Biotin, C3-symmetry, Dendrimers, Dendrons, Drug Carriers, Female, HSC70 Heat-Shock Proteins, HSPA8 protein, Humans, I2CT, Inbred MRL lpr, Lupus Erythematosus, Mice, P140 peptide, Peptide Fragments, Systemic, Team-Bianco
@article{lamanna_adamantane-based_2014,
title = {Adamantane-based dendrons for trimerization of the therapeutic P140 peptide},
author = {Giuseppe Lamanna and Maxime Grillaud and Christophe Macri and Olivier Chaloin and Sylviane Muller and Alberto Bianco},
doi = {10.1016/j.biomaterials.2014.05.017},
issn = {1878-5905},
year = {2014},
date = {2014-01-01},
journal = {Biomaterials},
volume = {35},
number = {26},
pages = {7553--7561},
abstract = {Dendrons constituted of an adamantane core, a focal point and three arms, were synthetized starting from a multifunctional adamantane derivative. Maleimido groups at the periphery of the scaffold were used to covalently attach the peptide called P140, a therapeutic phosphopeptide controlling disease activity in systemic lupus, both in mice and patients. Biotinylation of the trimers at the focal point was performed using click chemistry and the conjugates were studied in terms of solubility, binding affinity to its receptor, the HSPA8/HSC70 chaperone protein, effect on HSPA8 folding property and in vivo activity. The results showed that the trimerization of P140 peptide does not trigger aggregation or steric hindrances during the interaction with HSPA8 protein. Compared to the monomeric cognate peptide, the trivalent P140 peptide displayed the same capacity, in vitro, to down-regulate HSPA8 activity and, in vivo in MRL/lpr lupus-prone mice, to reduce abnormal blood hypercellularity. The control trimer synthesized with the same scaffold and a scrambled sequence of P140 showed no effect in vivo. This work reveals that adamantane-based scaffolds with a well-defined spatial conformation are promising trivalent systems for molecular recognition and for biomedical applications.},
keywords = {Adamantane, Animals, Biotin, C3-symmetry, Dendrimers, Dendrons, Drug Carriers, Female, HSC70 Heat-Shock Proteins, HSPA8 protein, Humans, I2CT, Inbred MRL lpr, Lupus Erythematosus, Mice, P140 peptide, Peptide Fragments, Systemic, Team-Bianco},
pubstate = {published},
tppubtype = {article}
}
2013
Schaeffer Evelyne, Dehuyser Laure, Sigwalt David, Flacher Vincent, Bernacchi Serena, Chaloin Olivier, Remy Jean-Serge, Mueller Christopher G, Baati Rachid, Wagner Alain
Dynamic micelles of mannoside glycolipids are more efficient than polymers for inhibiting HIV-1 trans-infection Article de journal
Dans: Bioconjugate Chemistry, vol. 24, no. 11, p. 1813–1823, 2013, ISSN: 1520-4812.
Résumé | Liens | BibTeX | Étiquettes: Anti-HIV Agents, Calcium, Cells, Chemistry, Cultured, Dendritic Cells, Dose-Response Relationship, Drug, Electron, fluorescence, Glycolipids, HIV, HIV Infections, HIV-1, Human, Humans, immunodeficiency, immunopathology, inhibition, LECTIN, Lectins, lipid, Mannosides, Micelles, Microbial Sensitivity Tests, Microscopy, Models, Molecular, Molecular Structure, Polymers, prophylaxis, Spectrometry, Structure-Activity Relationship, Surface Plasmon Resonance, target, Team-Mueller, Thermodynamics, Transmission, virus
@article{schaeffer_dynamic_2013,
title = {Dynamic micelles of mannoside glycolipids are more efficient than polymers for inhibiting HIV-1 trans-infection},
author = {Evelyne Schaeffer and Laure Dehuyser and David Sigwalt and Vincent Flacher and Serena Bernacchi and Olivier Chaloin and Jean-Serge Remy and Christopher G Mueller and Rachid Baati and Alain Wagner},
doi = {10.1021/bc4000806},
issn = {1520-4812},
year = {2013},
date = {2013-11-01},
journal = {Bioconjugate Chemistry},
volume = {24},
number = {11},
pages = {1813--1823},
abstract = {Mannoside glycolipid conjugates are able to inhibit human immunodeficiency virus type 1 (HIV-1) trans-infection mediated by human dendritic cells (DCs). The conjugates are formed by three building blocks: a linear or branched mannose head, a hydrophilic linker, and a 24-carbon lipid chain. We have shown that, even as single molecules, these compounds efficiently target mannose-binding lectins, such as DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN) important for HIV-1 transmission. With the goal to optimize their inhibitory activity by supramolecular structure formation, we have compared saturated and unsaturated conjugates, as single molecules, self-assemblies of dynamic micelles, and photopolymerized cross-linked polymers. Surface plasmon resonance showed that, unexpectedly, polymers of trivalent conjugates did not display a higher binding affinity for DC-SIGN than single molecules. Interactions on a chip or in solution were independent of calcium; however, binding to DCs was inhibited by a calcium chelator. Moreover, HIV-1 trans-infection was mostly inhibited by dynamic micelles and not by rigid polymers. The inhibition data revealed a clear correlation between the structure and molecular assembly of a conjugate and its biological antiviral activity. We present an interaction model between DC-SIGN and conjugates-either single molecules, micelles, or polymers-that highlights that the most effective interactions by dynamic micelles involve both mannose heads and lipid chains. Our data reveal that trivalent glycolipid conjugates display the highest microbicide potential for HIV prophylaxis, as dynamic micelles conjugates and not as rigid polymers.},
keywords = {Anti-HIV Agents, Calcium, Cells, Chemistry, Cultured, Dendritic Cells, Dose-Response Relationship, Drug, Electron, fluorescence, Glycolipids, HIV, HIV Infections, HIV-1, Human, Humans, immunodeficiency, immunopathology, inhibition, LECTIN, Lectins, lipid, Mannosides, Micelles, Microbial Sensitivity Tests, Microscopy, Models, Molecular, Molecular Structure, Polymers, prophylaxis, Spectrometry, Structure-Activity Relationship, Surface Plasmon Resonance, target, Team-Mueller, Thermodynamics, Transmission, virus},
pubstate = {published},
tppubtype = {article}
}
Fukuyama Hidehiro, Verdier Yann, Guan Yongsheng, Makino-Okamura Chieko, Shilova Victoria, Liu Xi, Maksoud Elie, Matsubayashi Jun, Haddad Iman, Spirohn Kerstin, Ono Kenichiro, Hetru Charles, Rossier Jean, Ideker Trey, Boutros Michael, Vinh Joëlle, Hoffmann Jules A
Landscape of protein-protein interactions in Drosophila immune deficiency signaling during bacterial challenge Article de journal
Dans: Proc. Natl. Acad. Sci. U.S.A., vol. 110, no. 26, p. 10717–10722, 2013, ISSN: 1091-6490.
Résumé | Liens | BibTeX | Étiquettes: Amino Acid, Animals, Chromatin Assembly and Disassembly, Escherichia coli, functional proteomics, Genes, Genetically Modified, Histone Acetyltransferases, hoffmann, Host-Pathogen Interactions, Humans, IMD interactome, Insect, M3i, Models, Molecular, Protein Interaction Maps, Sequence Homology, Signal Transduction, small ubiquitin-like modifier
@article{fukuyama_landscape_2013,
title = {Landscape of protein-protein interactions in Drosophila immune deficiency signaling during bacterial challenge},
author = {Hidehiro Fukuyama and Yann Verdier and Yongsheng Guan and Chieko Makino-Okamura and Victoria Shilova and Xi Liu and Elie Maksoud and Jun Matsubayashi and Iman Haddad and Kerstin Spirohn and Kenichiro Ono and Charles Hetru and Jean Rossier and Trey Ideker and Michael Boutros and Joëlle Vinh and Jules A Hoffmann},
doi = {10.1073/pnas.1304380110},
issn = {1091-6490},
year = {2013},
date = {2013-06-01},
journal = {Proc. Natl. Acad. Sci. U.S.A.},
volume = {110},
number = {26},
pages = {10717--10722},
abstract = {The Drosophila defense against pathogens largely relies on the activation of two signaling pathways: immune deficiency (IMD) and Toll. The IMD pathway is triggered mainly by Gram-negative bacteria, whereas the Toll pathway responds predominantly to Gram-positive bacteria and fungi. The activation of these pathways leads to the rapid induction of numerous NF-κB-induced immune response genes, including antimicrobial peptide genes. The IMD pathway shows significant similarities with the TNF receptor pathway. Recent evidence indicates that the IMD pathway is also activated in response to various noninfectious stimuli (i.e., inflammatory-like reactions). To gain a better understanding of the molecular machinery underlying the pleiotropic functions of this pathway, we first performed a comprehensive proteomics analysis to identify the proteins interacting with the 11 canonical members of the pathway initially identified by genetic studies. We identified 369 interacting proteins (corresponding to 291 genes) in heat-killed Escherichia coli-stimulated Drosophila S2 cells, 92% of which have human orthologs. A comparative analysis of gene ontology from fly or human gene annotation databases points to four significant common categories: (i) the NuA4, nucleosome acetyltransferase of H4, histone acetyltransferase complex, (ii) the switching defective/sucrose nonfermenting-type chromatin remodeling complex, (iii) transcription coactivator activity, and (iv) translation factor activity. Here we demonstrate that sumoylation of the IκB kinase homolog immune response-deficient 5 plays an important role in the induction of antimicrobial peptide genes through a highly conserved sumoylation consensus site during bacterial challenge. Taken together, the proteomics data presented here provide a unique avenue for a comparative functional analysis of proteins involved in innate immune reactions in flies and mammals.},
keywords = {Amino Acid, Animals, Chromatin Assembly and Disassembly, Escherichia coli, functional proteomics, Genes, Genetically Modified, Histone Acetyltransferases, hoffmann, Host-Pathogen Interactions, Humans, IMD interactome, Insect, M3i, Models, Molecular, Protein Interaction Maps, Sequence Homology, Signal Transduction, small ubiquitin-like modifier},
pubstate = {published},
tppubtype = {article}
}
Kobayashi Taira, Ogawa Michinaga, Sanada Takahito, Mimuro Hitomi, Kim Minsoo, Ashida Hiroshi, Akakura Reiko, Yoshida Mitsutaka, Kawalec Magdalena, Reichhart Jean-Marc, Mizushima Tsunehiro, Sasakawa Chihiro
The Shigella OspC3 effector inhibits caspase-4, antagonizes inflammatory cell death, and promotes epithelial infection Article de journal
Dans: Cell Host Microbe, vol. 13, no. 5, p. 570–583, 2013, ISSN: 1934-6069.
Résumé | Liens | BibTeX | Étiquettes: Animal, Animals, Bacillary, Bacterial, Bacterial Proteins, Caspases, Cell Death, Cell Line, Disease Models, DNA, Dysentery, Enzyme Inhibitors, Epithelial Cells, Escherichia coli, Gene Knockout Techniques, Guinea Pigs, Host-Pathogen Interactions, Humans, Initiator, M3i, Protein Binding, Protein Interaction Mapping, reichhart, Salmonella typhimurium, Sequence Analysis, Shigella flexneri, Virulence Factors
@article{kobayashi_shigella_2013,
title = {The Shigella OspC3 effector inhibits caspase-4, antagonizes inflammatory cell death, and promotes epithelial infection},
author = {Taira Kobayashi and Michinaga Ogawa and Takahito Sanada and Hitomi Mimuro and Minsoo Kim and Hiroshi Ashida and Reiko Akakura and Mitsutaka Yoshida and Magdalena Kawalec and Jean-Marc Reichhart and Tsunehiro Mizushima and Chihiro Sasakawa},
doi = {10.1016/j.chom.2013.04.012},
issn = {1934-6069},
year = {2013},
date = {2013-05-01},
journal = {Cell Host Microbe},
volume = {13},
number = {5},
pages = {570--583},
abstract = {Caspase-mediated inflammatory cell death acts as an intrinsic defense mechanism against infection. Bacterial pathogens deploy countermeasures against inflammatory cell death, but the mechanisms by which they do this remain largely unclear. In a screen for Shigella flexneri effectors that regulate cell death during infection, we discovered that Shigella infection induced acute inflammatory, caspase-4-dependent epithelial cell death, which is counteracted by the bacterial OspC3 effector. OspC3 interacts with the caspase-4-p19 subunit and inhibits its activation by preventing caspase-4-p19 and caspase-4-p10 heterodimerization by depositing the conserved OspC3 X1-Y-X₂-D-X₃ motif at the putative catalytic pocket of caspase-4. Infection of guinea pigs with a Shigella ospC3-deficient mutant resulted in enhanced inflammatory cell death and associated symptoms, correlating with decreased bacterial burdens. Salmonella Typhimurium and enteropathogenic Escherichia coli infection also induced caspase-4-dependent epithelial death. These findings highlight the importance of caspase-4-dependent innate immune responses and demonstrate that Shigella delivers a caspase-4-specific inhibitor to delay epithelial cell death and promote infection.},
keywords = {Animal, Animals, Bacillary, Bacterial, Bacterial Proteins, Caspases, Cell Death, Cell Line, Disease Models, DNA, Dysentery, Enzyme Inhibitors, Epithelial Cells, Escherichia coli, Gene Knockout Techniques, Guinea Pigs, Host-Pathogen Interactions, Humans, Initiator, M3i, Protein Binding, Protein Interaction Mapping, reichhart, Salmonella typhimurium, Sequence Analysis, Shigella flexneri, Virulence Factors},
pubstate = {published},
tppubtype = {article}
}
Ferrandon Dominique
The complementary facets of epithelial host defenses in the genetic model organism Drosophila melanogaster: from resistance to resilience Article de journal
Dans: Curr. Opin. Immunol., vol. 25, no. 1, p. 59–70, 2013, ISSN: 1879-0372.
Résumé | Liens | BibTeX | Étiquettes: Adult Stem Cells, aging, Animal, Animals, Cell Proliferation, Disease Models, Enterocytes, ferrandon, Humans, Immunity, Intestinal Mucosa, M3i, Metagenome, Stem Cell Niche, Wound Healing
@article{ferrandon_complementary_2013b,
title = {The complementary facets of epithelial host defenses in the genetic model organism Drosophila melanogaster: from resistance to resilience},
author = {Dominique Ferrandon},
doi = {10.1016/j.coi.2012.11.008},
issn = {1879-0372},
year = {2013},
date = {2013-02-01},
journal = {Curr. Opin. Immunol.},
volume = {25},
number = {1},
pages = {59--70},
abstract = {Significant advances have been made in our understanding of the host defense against microbial infections taking place at frontier epithelia of Drosophila flies. Immune deficiency (IMD), the major NF-κB immune response pathway induced in these epithelia, displays remarkable adaptations in its activation and regulation in the respiratory and digestive tract. The host defense against ingested pathogens is not limited to resistance, that is, the immune response. It also involves resilience, the capacity of the host to endure and repair damages inflicted by pathogens or the host's own immune response. For instance, enterocytes damaged by pathogens, the microbiota of aging flies, or host-derived reactive oxygen species (ROS), are replaced under the control of multiple pathways by the compensatory proliferation of intestinal stem cells (ISCs).},
keywords = {Adult Stem Cells, aging, Animal, Animals, Cell Proliferation, Disease Models, Enterocytes, ferrandon, Humans, Immunity, Intestinal Mucosa, M3i, Metagenome, Stem Cell Niche, Wound Healing},
pubstate = {published},
tppubtype = {article}
}
Coz Carole Le, Joublin Aurélie, Pasquali Jean-Louis, Korganow Anne-Sophie, Dumortier Hélène, Monneaux Fanny
Circulating TFH subset distribution is strongly affected in lupus patients with an active disease Article de journal
Dans: PloS One, vol. 8, no. 9, p. e75319, 2013, ISSN: 1932-6203.
Résumé | Liens | BibTeX | Étiquettes: Adult, Aged, B-Lymphocytes, Case-Control Studies, CD4 Lymphocyte Count, CD5 Antigens, CXCR5, Cytokines, Dumortier, Female, Flow Cytometry, Helper-Inducer, Humans, I2CT, Immunoglobulin E, Immunologic Memory, Immunophenotyping, Interleukin-21, Lupus Erythematosus, Male, Middle Aged, Monneaux, Phenotype, Receptors, Systemic, T-Lymphocytes, Team-Dumortier, Th2 Cells, Young Adult
@article{le_coz_circulating_2013,
title = {Circulating TFH subset distribution is strongly affected in lupus patients with an active disease},
author = {Carole Le Coz and Aurélie Joublin and Jean-Louis Pasquali and Anne-Sophie Korganow and Hélène Dumortier and Fanny Monneaux},
doi = {10.1371/journal.pone.0075319},
issn = {1932-6203},
year = {2013},
date = {2013-01-01},
journal = {PloS One},
volume = {8},
number = {9},
pages = {e75319},
abstract = {Follicular helper T cells (TFH) represent a distinct subset of CD4(+) T cells specialized in providing help to B lymphocytes, which may play a central role in autoimmune diseases having a major B cell component such as systemic lupus erythematosus. Recently, TFH subsets that share common phenotypic and functional characteristics with TFH cells from germinal centers, have been described in the peripheral blood from healthy individuals. The aim of this study was to analyze the distribution of such populations in lupus patients. Circulating TFH cell subsets were defined by multicolor flow cytometry as TFH17 (CXCR3(-)CCR6(+)), TFH1 (CXCR3 (+) CCR6(-)) or TFH2 (CXCR3(-)CCR6(-)) cells among CXCR5 (+) CD45RA(-)CD4(+) T cells in the peripheral blood of 23 SLE patients and 23 sex and age-matched healthy controls. IL-21 receptor expression by B cells was analyzed by flow cytometry and the serum levels of IL-21 and Igs were determined by ELISA tests. We found that the TFH2 cell subset frequency is strongly and significantly increased in lupus patients with an active disease (SLEDAI scoretextgreater8), while the TFH1 cell subset percentage is greatly decreased. The TFH2 and TFH1 cell subset frequency alteration is associated with the presence of high Ig levels and autoantibodies in patient's sera. Moreover, the TFH2 cell subset enhancement correlates with an increased frequency of double negative memory B cells (CD27(-)IgD(-)CD19(+) cells) expressing the IL-21R. Finally, we found that IgE levels in lupus patients' sera correlate with disease activity and seem to be associated with high TFH2 cell subset frequency. In conclusion, our study describes for the first time the distribution of circulating TFH cell subsets in lupus patients. Interestingly, we found an increased frequency of TFH2 cells, which correlates with disease activity. Our results suggest that this subset might play a key role in lupus pathogenesis.},
keywords = {Adult, Aged, B-Lymphocytes, Case-Control Studies, CD4 Lymphocyte Count, CD5 Antigens, CXCR5, Cytokines, Dumortier, Female, Flow Cytometry, Helper-Inducer, Humans, I2CT, Immunoglobulin E, Immunologic Memory, Immunophenotyping, Interleukin-21, Lupus Erythematosus, Male, Middle Aged, Monneaux, Phenotype, Receptors, Systemic, T-Lymphocytes, Team-Dumortier, Th2 Cells, Young Adult},
pubstate = {published},
tppubtype = {article}
}
Dumortier Hélène
When carbon nanotubes encounter the immune system: desirable and undesirable effects Article de journal
Dans: Advanced Drug Delivery Reviews, vol. 65, no. 15, p. 2120–2126, 2013, ISSN: 1872-8294.
Résumé | Liens | BibTeX | Étiquettes: Animals, Biomedical application, carbon, Carbon nanotubes, Dumortier, Environmental Exposure, Functionalization, Humans, I2CT, Immune cell activation, Immune System, inflammation, Inhalation Exposure, Lymphocyte, Macrophage, Nanotubes, Occupational Exposure, Team-Dumortier, Toxicity
@article{dumortier_when_2013,
title = {When carbon nanotubes encounter the immune system: desirable and undesirable effects},
author = {Hélène Dumortier},
doi = {10.1016/j.addr.2013.09.005},
issn = {1872-8294},
year = {2013},
date = {2013-01-01},
journal = {Advanced Drug Delivery Reviews},
volume = {65},
number = {15},
pages = {2120--2126},
abstract = {The role of our immune system is to bring efficient protection against invasion by foreign elements, not only pathogens but also any material it may be in contact with. Nanoparticles may enter the body and encounter the immune system either intentionally (e.g. administration for biomedical application) or not (e.g. respiratory occupational exposure). Therefore, it is of fundamental importance to get a thorough knowledge of the way they interact with immune cells and all related consequences. Among nanomaterials, carbon nanotubes (CNTs) are of special interest because of their tremendous field of applications. Consequently, their increasing production, processing and eventual incorporation into new types of composites and/or into biological systems have raised fundamental issues regarding their potential impact on health. This review aims at giving an overview of the known desirable and undesirable effects of CNTs on the immune system, i.e. beneficial modulation of immune cells by CNTs engineered for biomedical applications versus toxicity, inflammation and unwanted immune reactions triggered by CNTs themselves.},
keywords = {Animals, Biomedical application, carbon, Carbon nanotubes, Dumortier, Environmental Exposure, Functionalization, Humans, I2CT, Immune cell activation, Immune System, inflammation, Inhalation Exposure, Lymphocyte, Macrophage, Nanotubes, Occupational Exposure, Team-Dumortier, Toxicity},
pubstate = {published},
tppubtype = {article}
}
Russier Julie, Treossi Emanuele, Scarsi Alessia, Perrozzi Francesco, Dumortier Hélène, Ottaviano Luca, Meneghetti Moreno, Palermo Vincenzo, Bianco Alberto
Evidencing the mask effect of graphene oxide: a comparative study on primary human and murine phagocytic cells Article de journal
Dans: Nanoscale, vol. 5, no. 22, p. 11234–11247, 2013, ISSN: 2040-3372.
Résumé | Liens | BibTeX | Étiquettes: Animals, Cell Survival, Cells, Cultured, Cytokines, Dumortier, Graphite, Humans, I2CT, Macrophages, Mice, Monocytes, Oxidative Stress, Oxides, Reactive Oxygen Species, Team-Bianco, Team-Dumortier
@article{russier_evidencing_2013,
title = {Evidencing the mask effect of graphene oxide: a comparative study on primary human and murine phagocytic cells},
author = {Julie Russier and Emanuele Treossi and Alessia Scarsi and Francesco Perrozzi and Hélène Dumortier and Luca Ottaviano and Moreno Meneghetti and Vincenzo Palermo and Alberto Bianco},
doi = {10.1039/c3nr03543c},
issn = {2040-3372},
year = {2013},
date = {2013-01-01},
journal = {Nanoscale},
volume = {5},
number = {22},
pages = {11234--11247},
abstract = {Graphene oxide (GO) is attracting an ever-growing interest in different fields and applications. Not much is known about the possible impact of GO sheet lateral dimensions on their effects in vitro, especially on human primary cells. In an attempt to address this issue, we present a study to evaluate, how highly soluble 2-dimensional GO constituted of large or small flakes affects human monocyte derived macrophages (hMDM). For this purpose, the lateral size of GO was tuned using sonication and three samples were obtained. The non sonicated one presented large flakes (textasciitilde1.32 μm) while sonication for 2 and 26 hours generated small (textasciitilde0.27 μm) and very small (textasciitilde0.13 μm) sheets of GO, respectively. Cell studies were then conducted to evaluate the cytotoxicity, the oxidative stress induction, the activation potential and the pro-inflammatory effects of these different types of GO at increasing concentrations. In comparison, the same experiments were run on murine intraperitoneal macrophages (mIPM). The interaction between GO and cells was further examined by TEM and Raman spectroscopy. Our data revealed that the GO sheet size had a significant impact on different cellular parameters (i.e. cellular viability, ROS generation, and cellular activation). Indeed, the more the lateral dimensions of GO were reduced, the higher were the cellular internalization and the effects on cellular functionality. Our data also revealed a particular interaction of GO flakes with the cellular membrane. In fact, a GO mask due to the parallel arrangement of the graphene sheets on the cellular surface was observed. Considering the mask effect, we have hypothesized that this particular contact between GO sheets and the cell membrane could either promote their internalization or isolate cells from their environment, thus possibly accounting for the following impact on cellular parameters.},
keywords = {Animals, Cell Survival, Cells, Cultured, Cytokines, Dumortier, Graphite, Humans, I2CT, Macrophages, Mice, Monocytes, Oxidative Stress, Oxides, Reactive Oxygen Species, Team-Bianco, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
2012
Thomann Jean-Sébastien, Monneaux Fanny, Creusat Gaëlle, Spanedda Maria Vittoria, Heurtault Béatrice, Habermacher Chloé, Schuber Francis, Bourel-Bonnet Line, Frisch Benoît
Novel glycolipid TLR2 ligands of the type Pam2Cys-α-Gal: synthesis and biological properties Article de journal
Dans: European Journal of Medicinal Chemistry, vol. 51, p. 174–183, 2012, ISSN: 1768-3254.
Résumé | Liens | BibTeX | Étiquettes: Adjuvants, Animals, Cell Line, Chemistry Techniques, Female, Galactose, Glycolipids, Humans, I2CT, Immunologic, ligands, Mice, Monneaux, Structure-Activity Relationship, Synthetic, Team-Dumortier, Toll-Like Receptor 2
@article{thomann_novel_2012,
title = {Novel glycolipid TLR2 ligands of the type Pam2Cys-α-Gal: synthesis and biological properties},
author = {Jean-Sébastien Thomann and Fanny Monneaux and Gaëlle Creusat and Maria Vittoria Spanedda and Béatrice Heurtault and Chloé Habermacher and Francis Schuber and Line Bourel-Bonnet and Benoît Frisch},
doi = {10.1016/j.ejmech.2012.02.039},
issn = {1768-3254},
year = {2012},
date = {2012-05-01},
journal = {European Journal of Medicinal Chemistry},
volume = {51},
pages = {174--183},
abstract = {A more complete understanding of the mechanism of action of TLR agonists has fueled the investigation of new synthetic immunoadjuvants. In this context, we designed and synthesized glycolipids of the type Pam(2)Cys-α-Galactose as novel immunoadjuvants. Their synthesis required modifying a hydrophobic tBoc-[2,3-bispalmitoyloxy-(2R)-propyl]-R-cysteinyl moiety, i.e. the minimal structure required for TLR2 agonist activity, by addition of a hydrophilic head, either an α-Galactosylpyranose or an α-Galactosylfuranose to gain respectively Pam(2)CGalp and Pam(2)CGalf. While preparing a carbohydrate building block, an unexpected stereoselectivity was observed during a halide ion-catalytic process on a protected galactofuranose: the alpha anomer was obtained with surprisingly high selectivity (α/β ratiotextgreater9) and with good isolated yield (51%). The TLR2 binding properties of Pam(2)CGalp and Pam(2)CGalf were then fully evaluated. Their efficiency in triggering the proliferation of BALB/c mouse splenocytes was also compared to that of Pam(2)CAG and Pam(3)CAG, two well-established ligands of TLRs. Moreover, the maturation state of murine dendritic cells previously incubated with either Pam(2)CGalp or Pam(2)CGalf was monitored by flow cytometry and compared to that induced by lipopolysaccharide. Pam(2)CGalp and Pam(2)CGalf were found to be equivalent TLR2 agonists, and induced splenocyte proliferation and DC maturation. With very similar activity, Pam(2)CGalp and Pam(2)CGalf were also 10-fold to 100-fold better than Pam(2)CAG and Pam(3)CAG at inducing B cell proliferation. This represents the first time a glucidic head has been added to the tBoc-[2,3-bispalmitoyloxy-(2R)-propyl]-R-cysteinyl moiety whilst maintaining the immunomodulating activity. This should greatly enrich the data available on Pam(2)C structure/activity relationships.},
keywords = {Adjuvants, Animals, Cell Line, Chemistry Techniques, Female, Galactose, Glycolipids, Humans, I2CT, Immunologic, ligands, Mice, Monneaux, Structure-Activity Relationship, Synthetic, Team-Dumortier, Toll-Like Receptor 2},
pubstate = {published},
tppubtype = {article}
}
Delogu Lucia Gemma, Venturelli Enrica, Manetti Roberto, Pinna Gérard Aimé, Carru Ciriaco, Madeddu Roberto, Murgia Luciano, Sgarrella Francesco, Dumortier Hélène, Bianco Alberto
Ex vivo impact of functionalized carbon nanotubes on human immune cells Article de journal
Dans: Nanomedicine (London, England), vol. 7, no. 2, p. 231–243, 2012, ISSN: 1748-6963.
Résumé | Liens | BibTeX | Étiquettes: carbon, Cells, Cultured, Cytokines, Dumortier, Humans, I2CT, Immunity, Innate, Materials Testing, Nanotubes, T-Lymphocytes, Team-Bianco, Team-Dumortier
@article{delogu_ex_2012,
title = {Ex vivo impact of functionalized carbon nanotubes on human immune cells},
author = {Lucia Gemma Delogu and Enrica Venturelli and Roberto Manetti and Gérard Aimé Pinna and Ciriaco Carru and Roberto Madeddu and Luciano Murgia and Francesco Sgarrella and Hélène Dumortier and Alberto Bianco},
doi = {10.2217/nnm.11.101},
issn = {1748-6963},
year = {2012},
date = {2012-02-01},
journal = {Nanomedicine (London, England)},
volume = {7},
number = {2},
pages = {231--243},
abstract = {AIM: Different studies, carried out by us and others, have investigated the impact of carbon nanotubes (CNTs) in vitro and in animal models. To date, only a few studies have been performed on human cells ex vivo. There is also a lack of comparison between CNTs with varied functionalization and structural properties and their impact on different cell types.
MATERIALS & METHODS: The present ex vivo human study focuses on the impact of a series of functionalized multiwalled CNTs on human T and B lymphocytes, natural killer (NK) cells and monocytes.
RESULTS: Smaller diameter nanotubes are internalized more efficiently. Viability assays displayed the absence of cytotoxicity of all multiwalled CNTs used. Activation assay demonstrated a strong effect on monocytes and NK cells.
CONCLUSION: Our results, on human cells ex vivo, confirmed previous studies demonstrating appropriately functionalized CNTs are nontoxic. The effects on cell functionality were significant for the monocytes and NK cells. These findings encourage the possible use of CNTs for biomedical applications either as carriers of therapeutic molecules or as immune modulator systems.},
keywords = {carbon, Cells, Cultured, Cytokines, Dumortier, Humans, I2CT, Immunity, Innate, Materials Testing, Nanotubes, T-Lymphocytes, Team-Bianco, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
MATERIALS & METHODS: The present ex vivo human study focuses on the impact of a series of functionalized multiwalled CNTs on human T and B lymphocytes, natural killer (NK) cells and monocytes.
RESULTS: Smaller diameter nanotubes are internalized more efficiently. Viability assays displayed the absence of cytotoxicity of all multiwalled CNTs used. Activation assay demonstrated a strong effect on monocytes and NK cells.
CONCLUSION: Our results, on human cells ex vivo, confirmed previous studies demonstrating appropriately functionalized CNTs are nontoxic. The effects on cell functionality were significant for the monocytes and NK cells. These findings encourage the possible use of CNTs for biomedical applications either as carriers of therapeutic molecules or as immune modulator systems.
Meister Marie, Ferrandon Dominique
Immune cell transdifferentiation: a complex crosstalk between circulating immune cells and the haematopoietic niche Article de journal
Dans: EMBO Rep., vol. 13, no. 1, p. 3–4, 2012, ISSN: 1469-3178.
Liens | BibTeX | Étiquettes: Animals, Cell Communication, Cell Transdifferentiation, ferrandon, Hematopoietic Stem Cells, Humans, Immune System, M3i, Signal Transduction, Stem Cell Niche
@article{meister_immune_2012,
title = {Immune cell transdifferentiation: a complex crosstalk between circulating immune cells and the haematopoietic niche},
author = {Marie Meister and Dominique Ferrandon},
doi = {10.1038/embor.2011.238},
issn = {1469-3178},
year = {2012},
date = {2012-01-01},
journal = {EMBO Rep.},
volume = {13},
number = {1},
pages = {3--4},
keywords = {Animals, Cell Communication, Cell Transdifferentiation, ferrandon, Hematopoietic Stem Cells, Humans, Immune System, M3i, Signal Transduction, Stem Cell Niche},
pubstate = {published},
tppubtype = {article}
}
Schickel Jean-Nicolas, Pasquali Jean-Louis, Soley Anne, Knapp Anne-Marie, Decossas Marion, Kern Aurélie, Fauny Jean-Daniel, Marcellin Luc, Korganow Anne-Sophie, Martin Thierry, Soulas-Sprauel Pauline
Carabin deficiency in B cells increases BCR-TLR9 costimulation-induced autoimmunity Article de journal
Dans: EMBO molecular medicine, vol. 4, no. 12, p. 1261–1275, 2012, ISSN: 1757-4684.
Résumé | Liens | BibTeX | Étiquettes: Adaptor Proteins, Animals, Antigen, Autoimmunity, B-Cell, B-Lymphocytes, Carrier Proteins, Cohort Studies, DNA, Humans, I2CT, Imagerie, Inbred NZB, Inbred Strains, Mice, Phosphorylation, Prospective Studies, Receptors, Signal Transducing, Toll-Like Receptor 9, Transfection
@article{schickel_carabin_2012,
title = {Carabin deficiency in B cells increases BCR-TLR9 costimulation-induced autoimmunity},
author = {Jean-Nicolas Schickel and Jean-Louis Pasquali and Anne Soley and Anne-Marie Knapp and Marion Decossas and Aurélie Kern and Jean-Daniel Fauny and Luc Marcellin and Anne-Sophie Korganow and Thierry Martin and Pauline Soulas-Sprauel},
doi = {10.1002/emmm.201201595},
issn = {1757-4684},
year = {2012},
date = {2012-01-01},
journal = {EMBO molecular medicine},
volume = {4},
number = {12},
pages = {1261--1275},
abstract = {The mechanisms behind flares of human autoimmune diseases in general, and of systemic lupus in particular, are poorly understood. The present scenario proposes that predisposing gene defects favour clinical flares under the influence of external stimuli. Here, we show that Carabin is low in B cells of (NZB × NZW) F1 mice (murine SLE model) long before the disease onset, and is low in B cells of lupus patients during the inactive phases of the disease. Using knock-out and B-cell-conditional knock-out murine models, we identify Carabin as a new negative regulator of B-cell function, whose deficiency in B cells speeds up early B-cell responses and makes the mice more susceptible to anti-dsDNA production and renal lupus flare after stimulation with a Toll-like Receptor 9 agonist, CpG-DNA. Finally, in vitro analysis of NFκB activation and Erk phosphorylation in TLR9- and B-cell receptor (BCR)-stimulated Carabin-deficient B cells strongly suggests how the internal defect synergizes with the external stimulus and proposes Carabin as a natural inhibitor of the potentially dangerous crosstalk between BCR and TLR9 pathways in self-reactive B cells.},
keywords = {Adaptor Proteins, Animals, Antigen, Autoimmunity, B-Cell, B-Lymphocytes, Carrier Proteins, Cohort Studies, DNA, Humans, I2CT, Imagerie, Inbred NZB, Inbred Strains, Mice, Phosphorylation, Prospective Studies, Receptors, Signal Transducing, Toll-Like Receptor 9, Transfection},
pubstate = {published},
tppubtype = {article}
}
Keravis Thérèse, Monneaux Fanny, Yougbaré Issaka, Gazi Lucien, Bourguignon Jean-Jacques, Muller Sylviane, Lugnier Claire
Disease progression in MRL/lpr lupus-prone mice is reduced by NCS 613, a specific cyclic nucleotide phosphodiesterase type 4 (PDE4) inhibitor Article de journal
Dans: PloS One, vol. 7, no. 1, p. e28899, 2012, ISSN: 1932-6203.
Résumé | Liens | BibTeX | Étiquettes: Adenine, Animals, Cyclic AMP, Cyclic Nucleotide Phosphodiesterases, Disease Progression, Female, Humans, I2CT, Inbred CBA, Inbred MRL lpr, Isoenzymes, Kidney, Lipopolysaccharides, Lupus Erythematosus, Mice, Monneaux, Pentoxifylline, Phosphodiesterase 4 Inhibitors, Proteinuria, Survival Rate, Systemic, Team-Dumortier, Tumor Necrosis Factor-alpha, Type 4, Xanthines
@article{keravis_disease_2012,
title = {Disease progression in MRL/lpr lupus-prone mice is reduced by NCS 613, a specific cyclic nucleotide phosphodiesterase type 4 (PDE4) inhibitor},
author = {Thérèse Keravis and Fanny Monneaux and Issaka Yougbaré and Lucien Gazi and Jean-Jacques Bourguignon and Sylviane Muller and Claire Lugnier},
doi = {10.1371/journal.pone.0028899},
issn = {1932-6203},
year = {2012},
date = {2012-01-01},
journal = {PloS One},
volume = {7},
number = {1},
pages = {e28899},
abstract = {Systemic lupus erythematosus is a polymorphic and multigenic inflammatory autoimmune disease. Cyclic AMP (cAMP) modulates inflammation and the inhibition of cyclic nucleotide phosphodiesterase type 4 (PDE4), which specifically hydrolyzes cAMP, inhibits TNFα secretion. This study was aimed at investigating the evolution of PDE activity and expression levels during the course of the disease in MRL/lpr lupus-prone mice, and to evaluate in these mice the biological and clinical effects of treatments with pentoxifylline, denbufylline and NCS 613 PDE inhibitors. This study reveals that compared to CBA/J control mice, kidney PDE4 activity of MRL/lpr mice increases with the disease progression. Furthermore, it showed that the most potent and selective PDE4 inhibitor NCS 613 is also the most effective molecule in decreasing proteinuria and increasing survival rate of MRL/lpr mice. NCS 613 is a potent inhibitor, which is more selective for the PDE4C subtype (IC₅₀= 1.4 nM) than the other subtypes (PDE4A, IC₅₀= 44 nM; PDE4B, IC₅₀= 48 nM; and PDE4D, IC₅₀= 14 nM). Interestingly, its affinity for the High Affinity Rolipram Binding Site is relatively low (K(i) = 148 nM) in comparison to rolipram (K(i) = 3 nM). Finally, as also observed using MRL/lpr peripheral blood lymphocytes (PBLs), NCS 613 inhibits basal and LPS-induced TNFα secretion from PBLs of lupus patients, suggesting a therapeutic potential of NCS 613 in systemic lupus. This study reveals that PDE4 represent a potential therapeutic target in lupus disease.},
keywords = {Adenine, Animals, Cyclic AMP, Cyclic Nucleotide Phosphodiesterases, Disease Progression, Female, Humans, I2CT, Inbred CBA, Inbred MRL lpr, Isoenzymes, Kidney, Lipopolysaccharides, Lupus Erythematosus, Mice, Monneaux, Pentoxifylline, Phosphodiesterase 4 Inhibitors, Proteinuria, Survival Rate, Systemic, Team-Dumortier, Tumor Necrosis Factor-alpha, Type 4, Xanthines},
pubstate = {published},
tppubtype = {article}
}
Romani N, Flacher V, Tripp C H, Sparber F, Ebner S, Stoitzner P
Targeting skin dendritic cells to improve intradermal vaccination Article de journal
Dans: Current Topics in Microbiology and Immunology, vol. 351, p. 113–138, 2012, ISSN: 0070-217X.
Résumé | Liens | BibTeX | Étiquettes: Adaptive Immunity, administration & dosage, Analysis, Animals, Antibodies, antibody, Antigen, ANTIGEN PRESENTING CELLS, Antigen-Presenting Cells, Antigens, B CELLS, B-Lymphocytes, Bacterial Infections, Biosynthesis, C-Type, CD, CD14, CD1a, Cell Lineage, cytokine, Cytokines, cytology, Cytotoxic, Dendritic Cells, DERMATOLOGY, DERMIS, Drug Delivery Systems, Expression, Human, Humans, Immunity, Immunology, INDUCTION, Injections, Innate, Intradermal, Langerhans Cells, LECTIN, Lectins, Lymphocyte Activation, Lymphocytes, Mannose-Binding Lectins, methods, Mice, mouse, Muscle, prevention & control, PRODUCTION, Protein, review, Skin, SUBSETS, T-Lymphocytes, Team-Mueller, tolerance, Vaccination, vaccine, Vaccines, Virus Diseases
@article{romani_targeting_2012,
title = {Targeting skin dendritic cells to improve intradermal vaccination},
author = {N Romani and V Flacher and C H Tripp and F Sparber and S Ebner and P Stoitzner},
doi = {10.1007/82_2010_118},
issn = {0070-217X},
year = {2012},
date = {2012-01-01},
journal = {Current Topics in Microbiology and Immunology},
volume = {351},
pages = {113--138},
abstract = {Vaccinations in medicine are typically administered into the muscle beneath the skin or into the subcutaneous fat. As a consequence, the vaccine is immunologically processed by antigen-presenting cells of the skin or the muscle. Recent evidence suggests that the clinically seldom used intradermal route is effective and possibly even superior to the conventional subcutaneous or intramuscular route. Several types of professional antigen-presenting cells inhabit the healthy skin. Epidermal Langerhans cells (CD207/langerin(+)), dermal langerin(neg), and dermal langerin(+) dendritic cells (DC) have been described, the latter subset so far only in mouse skin. In human skin langerin(neg) dermal DC can be further classified based on their reciprocal expression of CD1a and CD14. The relative contributions of these subsets to the generation of immunity or tolerance are still unclear. Yet, specializations of these different populations have become apparent. Langerhans cells in human skin appear to be specialized for induction of cytotoxic T lymphocytes; human CD14(+) dermal DC can promote antibody production by B cells. It is currently attempted to rationally devise and improve vaccines by harnessing such specific properties of skin DC. This could be achieved by specifically targeting functionally diverse skin DC subsets. We discuss here advances in our knowledge on the immunological properties of skin DC and strategies to significantly improve the outcome of vaccinations by applying this knowledge.},
keywords = {Adaptive Immunity, administration & dosage, Analysis, Animals, Antibodies, antibody, Antigen, ANTIGEN PRESENTING CELLS, Antigen-Presenting Cells, Antigens, B CELLS, B-Lymphocytes, Bacterial Infections, Biosynthesis, C-Type, CD, CD14, CD1a, Cell Lineage, cytokine, Cytokines, cytology, Cytotoxic, Dendritic Cells, DERMATOLOGY, DERMIS, Drug Delivery Systems, Expression, Human, Humans, Immunity, Immunology, INDUCTION, Injections, Innate, Intradermal, Langerhans Cells, LECTIN, Lectins, Lymphocyte Activation, Lymphocytes, Mannose-Binding Lectins, methods, Mice, mouse, Muscle, prevention & control, PRODUCTION, Protein, review, Skin, SUBSETS, T-Lymphocytes, Team-Mueller, tolerance, Vaccination, vaccine, Vaccines, Virus Diseases},
pubstate = {published},
tppubtype = {article}
}
2011
Imler Jean-Luc, Ferrandon Dominique
[Innate immunity crowned 2011 Nobel Prize winner] Article de journal
Dans: Med Sci (Paris), vol. 27, p. 1019–24, 2011, ISSN: 0767-0974 (Print) 0767-0974 (Linking).
Liens | BibTeX | Étiquettes: *Immunity, *Nobel Prize, Biological, ferrandon, Genetic Association Studies, Humans, imler, Immunotherapy/methods/trends, Innate/genetics, M3i, Models, Molecular Targeted Therapy/trends, Seasons, Structure-Activity Relationship, Toll-Like Receptors/chemistry/genetics/isolation & purification/physiology
@article{imler_[innate_2011b,
title = {[Innate immunity crowned 2011 Nobel Prize winner]},
author = {Jean-Luc Imler and Dominique Ferrandon},
url = {http://dx.doi.org.gate1.inist.fr/10.1051/medsci/20112711020},
doi = {10.1051/medsci/20112711020},
issn = {0767-0974 (Print) 0767-0974 (Linking)},
year = {2011},
date = {2011-11-01},
journal = {Med Sci (Paris)},
volume = {27},
pages = {1019--24},
keywords = {*Immunity, *Nobel Prize, Biological, ferrandon, Genetic Association Studies, Humans, imler, Immunotherapy/methods/trends, Innate/genetics, M3i, Models, Molecular Targeted Therapy/trends, Seasons, Structure-Activity Relationship, Toll-Like Receptors/chemistry/genetics/isolation & purification/physiology},
pubstate = {published},
tppubtype = {article}
}
Ali-Boucetta Hanene, Al-Jamal Khuloud T, Müller Karin H, Li Shouping, Porter Alexandra E, Eddaoudi Ayad, Prato Maurizio, Bianco Alberto, Kostarelos Kostas
Cellular uptake and cytotoxic impact of chemically functionalized and polymer-coated carbon nanotubes Article de journal
Dans: Small (Weinheim an Der Bergstrasse, Germany), vol. 7, no. 22, p. 3230–3238, 2011, ISSN: 1613-6829.
Résumé | Liens | BibTeX | Étiquettes: Annexin A5, carbon, Cell Death, Cell Line, Endocytosis, Flow Cytometry, Fluorescein-5-isothiocyanate, Humans, I2CT, L-Lactate Dehydrogenase, mitochondria, Nanotubes, Polymers, Propidium, Surface Properties, Team-Bianco, tumor, water
@article{ali-boucetta_cellular_2011,
title = {Cellular uptake and cytotoxic impact of chemically functionalized and polymer-coated carbon nanotubes},
author = {Hanene Ali-Boucetta and Khuloud T Al-Jamal and Karin H Müller and Shouping Li and Alexandra E Porter and Ayad Eddaoudi and Maurizio Prato and Alberto Bianco and Kostas Kostarelos},
doi = {10.1002/smll.201101004},
issn = {1613-6829},
year = {2011},
date = {2011-11-01},
journal = {Small (Weinheim an Der Bergstrasse, Germany)},
volume = {7},
number = {22},
pages = {3230--3238},
abstract = {The impact of nanomaterials such as carbon nanotubes on biological matter is a topic of increasing interest and concern and requires a multifaceted approach to be resolved. A modified cytotoxic (lactate dehydrogenase (LDH)) assay is developed in an attempt to offer a valid and reliable methodology for screening carbon nanotube toxicity in vitro. Two of the most widely used types of surface-modified multiwalled carbon nanotubes (MWNTs) are tested: ammonium-functionalized MWNTs (MWNT-NH3+ ) and Pluronic F127 coated MWNTs (MWNT:F127). Chemically functionalized MWNTs show significantly greater cellular uptake into lung epithelial A549 cells compared to the non-covalently Pluronic F127-coated MWNTs. In spite of this, MWNT:F127 exhibit enhanced cytotoxicity according to the modified LDH assay. The validity of the modified LDH assay is further validated by direct comparison with other less reliable or accurate cytotoxicity assays. These findings indicate the reliability of the modified LDH assay as a screening tool to assess carbon nanotube cytotoxicity and illustrate that high levels of carbon nanotube cellular internalization do not necessarily lead to adverse responses.},
keywords = {Annexin A5, carbon, Cell Death, Cell Line, Endocytosis, Flow Cytometry, Fluorescein-5-isothiocyanate, Humans, I2CT, L-Lactate Dehydrogenase, mitochondria, Nanotubes, Polymers, Propidium, Surface Properties, Team-Bianco, tumor, water},
pubstate = {published},
tppubtype = {article}
}
Boyer Laurent, Magoc Lorin, Dejardin Stephanie, Cappillino Michael, Paquette Nicholas, Hinault Charlotte, Charriere Guillaume M, Ip Eddie W K, Fracchia Shannon, Hennessy Elizabeth, Erturk-Hasdemir Deniz, Reichhart Jean-Marc, Silverman Neal, Lacy-Hulbert Adam, Stuart Lynda M
Pathogen-derived effectors trigger protective immunity via activation of the Rac2 enzyme and the IMD or Rip kinase signaling pathway Article de journal
Dans: Immunity, vol. 35, no. 4, p. 536–549, 2011, ISSN: 1097-4180.
Résumé | Liens | BibTeX | Étiquettes: Adaptor Proteins, Enzyme Activation, HEK293 Cells, Humans, M3i, rac GTP-Binding Proteins, Receptor-Interacting Protein Serine-Threonine Kinases, reichhart, Signal Transducing, Signal Transduction
@article{boyer_pathogen-derived_2011,
title = {Pathogen-derived effectors trigger protective immunity via activation of the Rac2 enzyme and the IMD or Rip kinase signaling pathway},
author = {Laurent Boyer and Lorin Magoc and Stephanie Dejardin and Michael Cappillino and Nicholas Paquette and Charlotte Hinault and Guillaume M Charriere and Eddie W K Ip and Shannon Fracchia and Elizabeth Hennessy and Deniz Erturk-Hasdemir and Jean-Marc Reichhart and Neal Silverman and Adam Lacy-Hulbert and Lynda M Stuart},
doi = {10.1016/j.immuni.2011.08.015},
issn = {1097-4180},
year = {2011},
date = {2011-10-01},
journal = {Immunity},
volume = {35},
number = {4},
pages = {536--549},
abstract = {Although infections with virulent pathogens often induce a strong inflammatory reaction, what drives the increased immune response to pathogens compared to nonpathogenic microbes is poorly understood. One possibility is that the immune system senses the level of threat from a microorganism and augments the response accordingly. Here, focusing on cytotoxic necrotizing factor 1 (CNF1), an Escherichia coli-derived effector molecule, we showed the host indirectly sensed the pathogen by monitoring for the effector that modified RhoGTPases. CNF1 modified Rac2, which then interacted with the innate immune adaptors IMD and Rip1-Rip2 in flies and mammalian cells, respectively, to drive an immune response. This response was protective and increased the ability of the host to restrict pathogen growth, thus defining a mechanism of effector-triggered immunity that contributes to how metazoans defend against microbes with pathogenic potential.},
keywords = {Adaptor Proteins, Enzyme Activation, HEK293 Cells, Humans, M3i, rac GTP-Binding Proteins, Receptor-Interacting Protein Serine-Threonine Kinases, reichhart, Signal Transducing, Signal Transduction},
pubstate = {published},
tppubtype = {article}
}
Bianco Alberto, Kostarelos Kostas, Prato Maurizio
Making carbon nanotubes biocompatible and biodegradable Article de journal
Dans: Chemical Communications (Cambridge, England), vol. 47, no. 37, p. 10182–10188, 2011, ISSN: 1364-548X.
Résumé | Liens | BibTeX | Étiquettes: Animals, Biocompatible, carbon, Coated Materials, HeLa Cells, Humans, I2CT, nanotechnology, Nanotubes, Team-Bianco
@article{bianco_making_2011,
title = {Making carbon nanotubes biocompatible and biodegradable},
author = {Alberto Bianco and Kostas Kostarelos and Maurizio Prato},
doi = {10.1039/c1cc13011k},
issn = {1364-548X},
year = {2011},
date = {2011-10-01},
journal = {Chemical Communications (Cambridge, England)},
volume = {47},
number = {37},
pages = {10182--10188},
abstract = {Carbon nanotubes are promising nanomaterials with great potential in the field of nanomedicine for both therapeutic and diagnostic applications. Different approaches have been developed to render this material biocompatible and to modulate any ensuing toxic effects. In the context of medical use, although chemically functionalised carbon nanotubes display reduced toxicity, they are still considered with scepticism due to their perceived non-biodegradability. Recently, it has been demonstrated that functionalised carbon nanotubes can be degraded by oxidative enzymes. This finding is offering a new perspective for the development of carbon nanotubes in medicine. This article highlights recent advances that can act as paradigm-shifts towards the design of biocompatible and biodegradable functionalised carbon nanotubes and allow their translation into the clinic.},
keywords = {Animals, Biocompatible, carbon, Coated Materials, HeLa Cells, Humans, I2CT, nanotechnology, Nanotubes, Team-Bianco},
pubstate = {published},
tppubtype = {article}
}