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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}
}
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.
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}
}
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.
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}
}
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.
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}
}
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.
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}
}
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.
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}
}
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.
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}
}
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.
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}
}
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.
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}
}
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.
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}
}
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.
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}
}
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.
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}
}
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.
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}
}
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.
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}
}
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.
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}
}
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.
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}
}
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.
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}
}
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.
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}
}
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.
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}
}
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.
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}
}
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
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}
}
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.
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}
}
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.
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}
}
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.
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}
}
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.
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,