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2020
Spenlé Caroline, Loustau Thomas, Murdamoothoo Devadarssen, Erne William, la Forest Divonne Stephanie Beghelli-de, Veber Romain, Petti Luciana, Bourdely Pierre, Mörgelin Matthias, Brauchle Eva-Maria, Cremel Gérard, Randrianarisoa Vony, Camara Abdouramane, Rekima Samah, Schaub Sebastian, Nouhen Kelly, Imhof Thomas, Hansen Uwe, Paul Nicodème, Carapito Raphael, Pythoud Nicolas, Hirschler Aurélie, Carapito Christine, Dumortier Hélène, Mueller Christopher G, Koch Manuel, Schenke-Layland Katja, Kon Shigeyuki, Sudaka Anne, Anjuère Fabienne, Obberghen-Schilling Ellen Van, Orend Gertraud
Tenascin-C Orchestrates an Immune-Suppressive Tumor Microenvironment in Oral Squamous Cell Carcinoma Article de journal
Dans: Cancer Immunology Research, vol. 8, no. 9, p. 1122–1138, 2020, ISSN: 2326-6074.
Résumé | Liens | BibTeX | Étiquettes: Dumortier, I2CT, Team-Dumortier, Team-Mueller
@article{spenle_tenascin-c_2020,
title = {Tenascin-C Orchestrates an Immune-Suppressive Tumor Microenvironment in Oral Squamous Cell Carcinoma},
author = {Caroline Spenlé and Thomas Loustau and Devadarssen Murdamoothoo and William Erne and Stephanie Beghelli-de la Forest Divonne and Romain Veber and Luciana Petti and Pierre Bourdely and Matthias Mörgelin and Eva-Maria Brauchle and Gérard Cremel and Vony Randrianarisoa and Abdouramane Camara and Samah Rekima and Sebastian Schaub and Kelly Nouhen and Thomas Imhof and Uwe Hansen and Nicodème Paul and Raphael Carapito and Nicolas Pythoud and Aurélie Hirschler and Christine Carapito and Hélène Dumortier and Christopher G Mueller and Manuel Koch and Katja Schenke-Layland and Shigeyuki Kon and Anne Sudaka and Fabienne Anjuère and Ellen Van Obberghen-Schilling and Gertraud Orend},
doi = {10.1158/2326-6066.CIR-20-0074},
issn = {2326-6074},
year = {2020},
date = {2020-09-01},
journal = {Cancer Immunology Research},
volume = {8},
number = {9},
pages = {1122--1138},
abstract = {Inherent immune suppression represents a major challenge in the treatment of human cancer. The extracellular matrix molecule tenascin-C promotes cancer by multiple mechanisms, yet the roles of tenascin-C in tumor immunity are incompletely understood. Using a 4NQO-induced oral squamous cell carcinoma (OSCC) model with abundant and absent tenascin-C, we demonstrated that tenascin-C enforced an immune-suppressive lymphoid stroma via CCL21/CCR7 signaling, leading to increased metastatic tumors. Through TLR4, tenascin-C increased expression of CCR7 in CD11c+ myeloid cells. By inducing CCL21 in lymphatic endothelial cells via integrin α9β1 and binding to CCL21, tenascin-C immobilized CD11c+ cells in the stroma. Inversion of the lymph node-to-tumor CCL21 gradient, recruitment of T regulatory cells, high expression of anti-inflammatory cytokines, and matrisomal components were hallmarks of the tenascin-C-instructed lymphoid stroma. Ablation of tenascin-C or CCR7 blockade inhibited the lymphoid immune-suppressive stromal properties, reducing tumor growth, progression, and metastasis. Thus, targeting CCR7 could be relevant in human head and neck tumors, as high tenascin-C expression and an immune-suppressive stroma correlate to poor patient survival.},
keywords = {Dumortier, I2CT, Team-Dumortier, Team-Mueller},
pubstate = {published},
tppubtype = {article}
}
Inherent immune suppression represents a major challenge in the treatment of human cancer. The extracellular matrix molecule tenascin-C promotes cancer by multiple mechanisms, yet the roles of tenascin-C in tumor immunity are incompletely understood. Using a 4NQO-induced oral squamous cell carcinoma (OSCC) model with abundant and absent tenascin-C, we demonstrated that tenascin-C enforced an immune-suppressive lymphoid stroma via CCL21/CCR7 signaling, leading to increased metastatic tumors. Through TLR4, tenascin-C increased expression of CCR7 in CD11c+ myeloid cells. By inducing CCL21 in lymphatic endothelial cells via integrin α9β1 and binding to CCL21, tenascin-C immobilized CD11c+ cells in the stroma. Inversion of the lymph node-to-tumor CCL21 gradient, recruitment of T regulatory cells, high expression of anti-inflammatory cytokines, and matrisomal components were hallmarks of the tenascin-C-instructed lymphoid stroma. Ablation of tenascin-C or CCR7 blockade inhibited the lymphoid immune-suppressive stromal properties, reducing tumor growth, progression, and metastasis. Thus, targeting CCR7 could be relevant in human head and neck tumors, as high tenascin-C expression and an immune-suppressive stroma correlate to poor patient survival.
Malanagahalli Sowmya, Murera Diane, Martín Cristina, Lin Hazel, Wadier Nadége, Dumortier Hélène, Vázquez Ester, Bianco Alberto
Few Layer Graphene Does Not Affect Cellular Homeostasis of Mouse Macrophages Article de journal
Dans: Nanomaterials (Basel, Switzerland), vol. 10, no. 2, 2020, ISSN: 2079-4991.
Résumé | Liens | BibTeX | Étiquettes: Autophagy, bone marrow derived macrophages, carbon nanomaterials, Dumortier, graphene, I2CT, primary immune cells, Team-Bianco, Team-Dumortier
@article{malanagahalli_few_2020,
title = {Few Layer Graphene Does Not Affect Cellular Homeostasis of Mouse Macrophages},
author = {Sowmya Malanagahalli and Diane Murera and Cristina Martín and Hazel Lin and Nadége Wadier and Hélène Dumortier and Ester Vázquez and Alberto Bianco},
doi = {10.3390/nano10020228},
issn = {2079-4991},
year = {2020},
date = {2020-01-01},
journal = {Nanomaterials (Basel, Switzerland)},
volume = {10},
number = {2},
abstract = {: Graphene-related materials (GRMs) are widely used in various applications due to their unique properties. A growing number of reports describe the impact of different carbon nanomaterials, including graphene oxide (GO), reduced GO (rGO), and carbon nanotubes (CNT), on immune cells, but there is still a very limited number of studies on graphene. In this work, we investigated the biological responses of few layer graphene (FLG) on mouse macrophages (bone marrow derived macrophages, BMDMs), which are part of the first line of defense in innate immunity. In particular, our paper describes our findings of short-term FLG treatment in BMDMs with a focus on observing material internalization and changes in general cell morphology. Subsequent investigation of cytotoxicity parameters showed that increasing doses of FLG did not hamper the viability of cells and did not trigger inflammatory responses. Basal level induced autophagic activity sufficed to maintain the cellular homeostasis of FLG treated cells. Our results shed light on the impact of FLG on primary macrophages and show that FLG does not elicit immunological responses leading to cell death.},
keywords = {Autophagy, bone marrow derived macrophages, carbon nanomaterials, Dumortier, graphene, I2CT, primary immune cells, Team-Bianco, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
: Graphene-related materials (GRMs) are widely used in various applications due to their unique properties. A growing number of reports describe the impact of different carbon nanomaterials, including graphene oxide (GO), reduced GO (rGO), and carbon nanotubes (CNT), on immune cells, but there is still a very limited number of studies on graphene. In this work, we investigated the biological responses of few layer graphene (FLG) on mouse macrophages (bone marrow derived macrophages, BMDMs), which are part of the first line of defense in innate immunity. In particular, our paper describes our findings of short-term FLG treatment in BMDMs with a focus on observing material internalization and changes in general cell morphology. Subsequent investigation of cytotoxicity parameters showed that increasing doses of FLG did not hamper the viability of cells and did not trigger inflammatory responses. Basal level induced autophagic activity sufficed to maintain the cellular homeostasis of FLG treated cells. Our results shed light on the impact of FLG on primary macrophages and show that FLG does not elicit immunological responses leading to cell death.
2019
Murera Diane, Malaganahalli Sowmya, Martín Cristina, Reina Giacomo, Fauny Jean-Daniel, Dumortier Hélène, Vázquez Ester, Bianco Alberto
Few layer graphene does not affect the function and the autophagic activity of primary lymphocytes Article de journal
Dans: Nanoscale, vol. 11, no. 21, p. 10493–10503, 2019, ISSN: 2040-3372.
Résumé | Liens | BibTeX | Étiquettes: Animals, Autophagy, B-Lymphocytes, Dumortier, Graphite, I2CT, Inbred BALB C, Mice, Nanostructures, T-Lymphocytes, Team-Bianco, Team-Dumortier
@article{murera_few_2019,
title = {Few layer graphene does not affect the function and the autophagic activity of primary lymphocytes},
author = {Diane Murera and Sowmya Malaganahalli and Cristina Martín and Giacomo Reina and Jean-Daniel Fauny and Hélène Dumortier and Ester Vázquez and Alberto Bianco},
doi = {10.1039/c9nr00846b},
issn = {2040-3372},
year = {2019},
date = {2019-01-01},
journal = {Nanoscale},
volume = {11},
number = {21},
pages = {10493--10503},
abstract = {Carbon-based nanomaterials represent a new tool in future medical applications. Thus, focusing on the evaluation of the degree of their safety has been growing in the last years. In this study we were particularly interested in understanding the impact of few layer graphene (FLG) on primary murine lymphocytes. These B and T cells, that are the second, but specialized, line of defense of the immune system, rely on various mechanisms to ensure their efficient function and maintenance. One of these mechanisms is autophagy that can be triggered by various nanomaterials in some types of cells. For these reasons, we were interested in evaluating the way FLG could affect this process in lymphocytes. Our results point out that FLG neither impacts the viability and activation of T and B cells nor their autophagic activity. Using confocal microscopy, we were also able to see that FLG does not appear to cause any membrane damage and does not penetrate inside of these cells. Overall, our data do not show any effect of this material on lymphocyte homeostasis, which is one more argument in favor of the continuation of studies investigating the potential of FLG for therapeutic applications.},
keywords = {Animals, Autophagy, B-Lymphocytes, Dumortier, Graphite, I2CT, Inbred BALB C, Mice, Nanostructures, T-Lymphocytes, Team-Bianco, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
Carbon-based nanomaterials represent a new tool in future medical applications. Thus, focusing on the evaluation of the degree of their safety has been growing in the last years. In this study we were particularly interested in understanding the impact of few layer graphene (FLG) on primary murine lymphocytes. These B and T cells, that are the second, but specialized, line of defense of the immune system, rely on various mechanisms to ensure their efficient function and maintenance. One of these mechanisms is autophagy that can be triggered by various nanomaterials in some types of cells. For these reasons, we were interested in evaluating the way FLG could affect this process in lymphocytes. Our results point out that FLG neither impacts the viability and activation of T and B cells nor their autophagic activity. Using confocal microscopy, we were also able to see that FLG does not appear to cause any membrane damage and does not penetrate inside of these cells. Overall, our data do not show any effect of this material on lymphocyte homeostasis, which is one more argument in favor of the continuation of studies investigating the potential of FLG for therapeutic applications.
2018
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.
2017
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: Dumortier, I2CT, Imagerie, Team-Dumortier
@article{gies_identification_2017,
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 = {2017-04-01},
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 = {Dumortier, I2CT, Imagerie, 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.
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.
2016
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.
2015
Jacquemin Clément, Schmitt Nathalie, Contin-Bordes Cécile, Liu Yang, Narayanan Priya, Seneschal Julien, Maurouard Typhanie, Dougall David, Davizon Emily Spence, Dumortier Hélène, Douchet Isabelle, Raffray Loïc, Richez Christophe, Lazaro Estibaliz, Duffau Pierre, Truchetet Marie-Elise, Khoryati Liliane, Mercié Patrick, Couzi Lionel, Merville Pierre, Schaeverbeke Thierry, Viallard Jean-François, Pellegrin Jean-Luc, Moreau Jean-François, Muller Sylviane, Zurawski Sandy, Coffman Robert L, Pascual Virginia, Ueno Hideki, Blanco Patrick
OX40 Ligand Contributes to Human Lupus Pathogenesis by Promoting Ŧ Follicular Helper Response Article de journal
Dans: Immunity, vol. 42, no. 6, p. 1159–1170, 2015, ISSN: 1097-4180.
Résumé | Liens | BibTeX | Étiquettes: Adolescent, Adult, Aged, Antigen Presentation, B-Lymphocytes, Cell Differentiation, Cells, Cultured, Cytokines, Disease Progression, Dumortier, Female, Helper-Inducer, Humans, I2CT, Immunologic Memory, Inducible T-Cell Co-Stimulator Protein, Lupus Erythematosus, Lymphocyte Activation, Male, Middle Aged, Molecular Targeted Therapy, Myeloid Cells, OX40, OX40 Ligand, Receptors, RNA, Signal Transduction, Systemic, T-Lymphocytes, Team-Dumortier, Toll-Like Receptor 7, Young Adult
@article{jacquemin_ox40_2015,
title = {OX40 Ligand Contributes to Human Lupus Pathogenesis by Promoting Ŧ Follicular Helper Response},
author = {Clément Jacquemin and Nathalie Schmitt and Cécile Contin-Bordes and Yang Liu and Priya Narayanan and Julien Seneschal and Typhanie Maurouard and David Dougall and Emily Spence Davizon and Hélène Dumortier and Isabelle Douchet and Loïc Raffray and Christophe Richez and Estibaliz Lazaro and Pierre Duffau and Marie-Elise Truchetet and Liliane Khoryati and Patrick Mercié and Lionel Couzi and Pierre Merville and Thierry Schaeverbeke and Jean-François Viallard and Jean-Luc Pellegrin and Jean-François Moreau and Sylviane Muller and Sandy Zurawski and Robert L Coffman and Virginia Pascual and Hideki Ueno and Patrick Blanco},
doi = {10.1016/j.immuni.2015.05.012},
issn = {1097-4180},
year = {2015},
date = {2015-01-01},
journal = {Immunity},
volume = {42},
number = {6},
pages = {1159--1170},
abstract = {Increased activity of T follicular helper (Tfh) cells plays a major pathogenic role in systemic lupus erythematosus (SLE). However, the mechanisms that cause aberrant Tfh cell responses in SLE remain elusive. Here we showed the OX40 ligand (OX40L)-OX40 axis contributes to the aberrant Tfh response in SLE. OX40L was expressed by myeloid antigen-presenting cells (APCs), but not B cells, in blood and in inflamed tissues in adult and pediatric SLE patients. The frequency of circulating OX40L-expressing myeloid APCs positively correlated with disease activity and the frequency of ICOS(+) blood Tfh cells in SLE. OX40 signals promoted naive and memory CD4(+) T cells to express multiple Tfh cell molecules and were sufficient to induce them to become functional B cell helpers. Immune complexes containing RNA induced OX40L expression on myeloid APCs via TLR7 activation. Our study provides a rationale to target the OX40L-OX40 axis as a therapeutic modality for SLE.},
keywords = {Adolescent, Adult, Aged, Antigen Presentation, B-Lymphocytes, Cell Differentiation, Cells, Cultured, Cytokines, Disease Progression, Dumortier, Female, Helper-Inducer, Humans, I2CT, Immunologic Memory, Inducible T-Cell Co-Stimulator Protein, Lupus Erythematosus, Lymphocyte Activation, Male, Middle Aged, Molecular Targeted Therapy, Myeloid Cells, OX40, OX40 Ligand, Receptors, RNA, Signal Transduction, Systemic, T-Lymphocytes, Team-Dumortier, Toll-Like Receptor 7, Young Adult},
pubstate = {published},
tppubtype = {article}
}
Increased activity of T follicular helper (Tfh) cells plays a major pathogenic role in systemic lupus erythematosus (SLE). However, the mechanisms that cause aberrant Tfh cell responses in SLE remain elusive. Here we showed the OX40 ligand (OX40L)-OX40 axis contributes to the aberrant Tfh response in SLE. OX40L was expressed by myeloid antigen-presenting cells (APCs), but not B cells, in blood and in inflamed tissues in adult and pediatric SLE patients. The frequency of circulating OX40L-expressing myeloid APCs positively correlated with disease activity and the frequency of ICOS(+) blood Tfh cells in SLE. OX40 signals promoted naive and memory CD4(+) T cells to express multiple Tfh cell molecules and were sufficient to induce them to become functional B cell helpers. Immune complexes containing RNA induced OX40L expression on myeloid APCs via TLR7 activation. Our study provides a rationale to target the OX40L-OX40 axis as a therapeutic modality for SLE.
2013
Coz Carole Le, Joublin Aurélie, Pasquali Jean-Louis, Korganow Anne-Sophie, Dumortier Hélène, Monneaux Fanny
Circulating TFH subset distribution is strongly affected in lupus patients with an active disease Article de journal
Dans: PloS One, vol. 8, no. 9, p. e75319, 2013, ISSN: 1932-6203.
Résumé | Liens | BibTeX | Étiquettes: Adult, Aged, B-Lymphocytes, Case-Control Studies, CD4 Lymphocyte Count, CD5 Antigens, CXCR5, Cytokines, Dumortier, Female, Flow Cytometry, Helper-Inducer, Humans, I2CT, Immunoglobulin E, Immunologic Memory, Immunophenotyping, Interleukin-21, Lupus Erythematosus, Male, Middle Aged, Monneaux, Phenotype, Receptors, Systemic, T-Lymphocytes, Team-Dumortier, Th2 Cells, Young Adult
@article{le_coz_circulating_2013,
title = {Circulating TFH subset distribution is strongly affected in lupus patients with an active disease},
author = {Carole Le Coz and Aurélie Joublin and Jean-Louis Pasquali and Anne-Sophie Korganow and Hélène Dumortier and Fanny Monneaux},
doi = {10.1371/journal.pone.0075319},
issn = {1932-6203},
year = {2013},
date = {2013-01-01},
journal = {PloS One},
volume = {8},
number = {9},
pages = {e75319},
abstract = {Follicular helper T cells (TFH) represent a distinct subset of CD4(+) T cells specialized in providing help to B lymphocytes, which may play a central role in autoimmune diseases having a major B cell component such as systemic lupus erythematosus. Recently, TFH subsets that share common phenotypic and functional characteristics with TFH cells from germinal centers, have been described in the peripheral blood from healthy individuals. The aim of this study was to analyze the distribution of such populations in lupus patients. Circulating TFH cell subsets were defined by multicolor flow cytometry as TFH17 (CXCR3(-)CCR6(+)), TFH1 (CXCR3 (+) CCR6(-)) or TFH2 (CXCR3(-)CCR6(-)) cells among CXCR5 (+) CD45RA(-)CD4(+) T cells in the peripheral blood of 23 SLE patients and 23 sex and age-matched healthy controls. IL-21 receptor expression by B cells was analyzed by flow cytometry and the serum levels of IL-21 and Igs were determined by ELISA tests. We found that the TFH2 cell subset frequency is strongly and significantly increased in lupus patients with an active disease (SLEDAI scoretextgreater8), while the TFH1 cell subset percentage is greatly decreased. The TFH2 and TFH1 cell subset frequency alteration is associated with the presence of high Ig levels and autoantibodies in patient's sera. Moreover, the TFH2 cell subset enhancement correlates with an increased frequency of double negative memory B cells (CD27(-)IgD(-)CD19(+) cells) expressing the IL-21R. Finally, we found that IgE levels in lupus patients' sera correlate with disease activity and seem to be associated with high TFH2 cell subset frequency. In conclusion, our study describes for the first time the distribution of circulating TFH cell subsets in lupus patients. Interestingly, we found an increased frequency of TFH2 cells, which correlates with disease activity. Our results suggest that this subset might play a key role in lupus pathogenesis.},
keywords = {Adult, Aged, B-Lymphocytes, Case-Control Studies, CD4 Lymphocyte Count, CD5 Antigens, CXCR5, Cytokines, Dumortier, Female, Flow Cytometry, Helper-Inducer, Humans, I2CT, Immunoglobulin E, Immunologic Memory, Immunophenotyping, Interleukin-21, Lupus Erythematosus, Male, Middle Aged, Monneaux, Phenotype, Receptors, Systemic, T-Lymphocytes, Team-Dumortier, Th2 Cells, Young Adult},
pubstate = {published},
tppubtype = {article}
}
Follicular helper T cells (TFH) represent a distinct subset of CD4(+) T cells specialized in providing help to B lymphocytes, which may play a central role in autoimmune diseases having a major B cell component such as systemic lupus erythematosus. Recently, TFH subsets that share common phenotypic and functional characteristics with TFH cells from germinal centers, have been described in the peripheral blood from healthy individuals. The aim of this study was to analyze the distribution of such populations in lupus patients. Circulating TFH cell subsets were defined by multicolor flow cytometry as TFH17 (CXCR3(-)CCR6(+)), TFH1 (CXCR3 (+) CCR6(-)) or TFH2 (CXCR3(-)CCR6(-)) cells among CXCR5 (+) CD45RA(-)CD4(+) T cells in the peripheral blood of 23 SLE patients and 23 sex and age-matched healthy controls. IL-21 receptor expression by B cells was analyzed by flow cytometry and the serum levels of IL-21 and Igs were determined by ELISA tests. We found that the TFH2 cell subset frequency is strongly and significantly increased in lupus patients with an active disease (SLEDAI scoretextgreater8), while the TFH1 cell subset percentage is greatly decreased. The TFH2 and TFH1 cell subset frequency alteration is associated with the presence of high Ig levels and autoantibodies in patient's sera. Moreover, the TFH2 cell subset enhancement correlates with an increased frequency of double negative memory B cells (CD27(-)IgD(-)CD19(+) cells) expressing the IL-21R. Finally, we found that IgE levels in lupus patients' sera correlate with disease activity and seem to be associated with high TFH2 cell subset frequency. In conclusion, our study describes for the first time the distribution of circulating TFH cell subsets in lupus patients. Interestingly, we found an increased frequency of TFH2 cells, which correlates with disease activity. Our results suggest that this subset might play a key role in lupus pathogenesis.
Dumortier Hélène
When carbon nanotubes encounter the immune system: desirable and undesirable effects Article de journal
Dans: Advanced Drug Delivery Reviews, vol. 65, no. 15, p. 2120–2126, 2013, ISSN: 1872-8294.
Résumé | Liens | BibTeX | Étiquettes: Animals, Biomedical application, carbon, Carbon nanotubes, Dumortier, Environmental Exposure, Functionalization, Humans, I2CT, Immune cell activation, Immune System, inflammation, Inhalation Exposure, Lymphocyte, Macrophage, Nanotubes, Occupational Exposure, Team-Dumortier, Toxicity
@article{dumortier_when_2013,
title = {When carbon nanotubes encounter the immune system: desirable and undesirable effects},
author = {Hélène Dumortier},
doi = {10.1016/j.addr.2013.09.005},
issn = {1872-8294},
year = {2013},
date = {2013-01-01},
journal = {Advanced Drug Delivery Reviews},
volume = {65},
number = {15},
pages = {2120--2126},
abstract = {The role of our immune system is to bring efficient protection against invasion by foreign elements, not only pathogens but also any material it may be in contact with. Nanoparticles may enter the body and encounter the immune system either intentionally (e.g. administration for biomedical application) or not (e.g. respiratory occupational exposure). Therefore, it is of fundamental importance to get a thorough knowledge of the way they interact with immune cells and all related consequences. Among nanomaterials, carbon nanotubes (CNTs) are of special interest because of their tremendous field of applications. Consequently, their increasing production, processing and eventual incorporation into new types of composites and/or into biological systems have raised fundamental issues regarding their potential impact on health. This review aims at giving an overview of the known desirable and undesirable effects of CNTs on the immune system, i.e. beneficial modulation of immune cells by CNTs engineered for biomedical applications versus toxicity, inflammation and unwanted immune reactions triggered by CNTs themselves.},
keywords = {Animals, Biomedical application, carbon, Carbon nanotubes, Dumortier, Environmental Exposure, Functionalization, Humans, I2CT, Immune cell activation, Immune System, inflammation, Inhalation Exposure, Lymphocyte, Macrophage, Nanotubes, Occupational Exposure, Team-Dumortier, Toxicity},
pubstate = {published},
tppubtype = {article}
}
The role of our immune system is to bring efficient protection against invasion by foreign elements, not only pathogens but also any material it may be in contact with. Nanoparticles may enter the body and encounter the immune system either intentionally (e.g. administration for biomedical application) or not (e.g. respiratory occupational exposure). Therefore, it is of fundamental importance to get a thorough knowledge of the way they interact with immune cells and all related consequences. Among nanomaterials, carbon nanotubes (CNTs) are of special interest because of their tremendous field of applications. Consequently, their increasing production, processing and eventual incorporation into new types of composites and/or into biological systems have raised fundamental issues regarding their potential impact on health. This review aims at giving an overview of the known desirable and undesirable effects of CNTs on the immune system, i.e. beneficial modulation of immune cells by CNTs engineered for biomedical applications versus toxicity, inflammation and unwanted immune reactions triggered by CNTs themselves.
Russier Julie, Treossi Emanuele, Scarsi Alessia, Perrozzi Francesco, Dumortier Hélène, Ottaviano Luca, Meneghetti Moreno, Palermo Vincenzo, Bianco Alberto
Evidencing the mask effect of graphene oxide: a comparative study on primary human and murine phagocytic cells Article de journal
Dans: Nanoscale, vol. 5, no. 22, p. 11234–11247, 2013, ISSN: 2040-3372.
Résumé | Liens | BibTeX | Étiquettes: Animals, Cell Survival, Cells, Cultured, Cytokines, Dumortier, Graphite, Humans, I2CT, Macrophages, Mice, Monocytes, Oxidative Stress, Oxides, Reactive Oxygen Species, Team-Bianco, Team-Dumortier
@article{russier_evidencing_2013,
title = {Evidencing the mask effect of graphene oxide: a comparative study on primary human and murine phagocytic cells},
author = {Julie Russier and Emanuele Treossi and Alessia Scarsi and Francesco Perrozzi and Hélène Dumortier and Luca Ottaviano and Moreno Meneghetti and Vincenzo Palermo and Alberto Bianco},
doi = {10.1039/c3nr03543c},
issn = {2040-3372},
year = {2013},
date = {2013-01-01},
journal = {Nanoscale},
volume = {5},
number = {22},
pages = {11234--11247},
abstract = {Graphene oxide (GO) is attracting an ever-growing interest in different fields and applications. Not much is known about the possible impact of GO sheet lateral dimensions on their effects in vitro, especially on human primary cells. In an attempt to address this issue, we present a study to evaluate, how highly soluble 2-dimensional GO constituted of large or small flakes affects human monocyte derived macrophages (hMDM). For this purpose, the lateral size of GO was tuned using sonication and three samples were obtained. The non sonicated one presented large flakes (textasciitilde1.32 μm) while sonication for 2 and 26 hours generated small (textasciitilde0.27 μm) and very small (textasciitilde0.13 μm) sheets of GO, respectively. Cell studies were then conducted to evaluate the cytotoxicity, the oxidative stress induction, the activation potential and the pro-inflammatory effects of these different types of GO at increasing concentrations. In comparison, the same experiments were run on murine intraperitoneal macrophages (mIPM). The interaction between GO and cells was further examined by TEM and Raman spectroscopy. Our data revealed that the GO sheet size had a significant impact on different cellular parameters (i.e. cellular viability, ROS generation, and cellular activation). Indeed, the more the lateral dimensions of GO were reduced, the higher were the cellular internalization and the effects on cellular functionality. Our data also revealed a particular interaction of GO flakes with the cellular membrane. In fact, a GO mask due to the parallel arrangement of the graphene sheets on the cellular surface was observed. Considering the mask effect, we have hypothesized that this particular contact between GO sheets and the cell membrane could either promote their internalization or isolate cells from their environment, thus possibly accounting for the following impact on cellular parameters.},
keywords = {Animals, Cell Survival, Cells, Cultured, Cytokines, Dumortier, Graphite, Humans, I2CT, Macrophages, Mice, Monocytes, Oxidative Stress, Oxides, Reactive Oxygen Species, Team-Bianco, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
Graphene oxide (GO) is attracting an ever-growing interest in different fields and applications. Not much is known about the possible impact of GO sheet lateral dimensions on their effects in vitro, especially on human primary cells. In an attempt to address this issue, we present a study to evaluate, how highly soluble 2-dimensional GO constituted of large or small flakes affects human monocyte derived macrophages (hMDM). For this purpose, the lateral size of GO was tuned using sonication and three samples were obtained. The non sonicated one presented large flakes (textasciitilde1.32 μm) while sonication for 2 and 26 hours generated small (textasciitilde0.27 μm) and very small (textasciitilde0.13 μm) sheets of GO, respectively. Cell studies were then conducted to evaluate the cytotoxicity, the oxidative stress induction, the activation potential and the pro-inflammatory effects of these different types of GO at increasing concentrations. In comparison, the same experiments were run on murine intraperitoneal macrophages (mIPM). The interaction between GO and cells was further examined by TEM and Raman spectroscopy. Our data revealed that the GO sheet size had a significant impact on different cellular parameters (i.e. cellular viability, ROS generation, and cellular activation). Indeed, the more the lateral dimensions of GO were reduced, the higher were the cellular internalization and the effects on cellular functionality. Our data also revealed a particular interaction of GO flakes with the cellular membrane. In fact, a GO mask due to the parallel arrangement of the graphene sheets on the cellular surface was observed. Considering the mask effect, we have hypothesized that this particular contact between GO sheets and the cell membrane could either promote their internalization or isolate cells from their environment, thus possibly accounting for the following impact on cellular parameters.
Lacotte Stéphanie, Decossas Marion, Coz Carole Le, Brun Susana, Muller Sylviane, Dumortier Hélène
Early differentiated CD138(high) MHCII+ IgG+ plasma cells express CXCR3 and localize into inflamed kidneys of lupus mice Article de journal
Dans: PloS One, vol. 8, no. 3, p. e58140, 2013, ISSN: 1932-6203.
Résumé | Liens | BibTeX | Étiquettes: Animals, Autoantibodies, Cell Differentiation, CXCR3, Dumortier, Gene Expression Regulation, Histocompatibility Antigens Class II, I2CT, Immunoglobulin G, Inbred BALB C, Kidney, Leukocyte Common Antigens, Lupus Nephritis, Mice, Plasma Cells, Receptors, Syndecan-1, Team-Dumortier
@article{lacotte_early_2013,
title = {Early differentiated CD138(high) MHCII+ IgG+ plasma cells express CXCR3 and localize into inflamed kidneys of lupus mice},
author = {Stéphanie Lacotte and Marion Decossas and Carole Le Coz and Susana Brun and Sylviane Muller and Hélène Dumortier},
doi = {10.1371/journal.pone.0058140},
issn = {1932-6203},
year = {2013},
date = {2013-01-01},
journal = {PloS One},
volume = {8},
number = {3},
pages = {e58140},
abstract = {Humoral responses are central to the development of chronic autoimmune diseases such as systemic lupus erythematosus. Indeed, autoantibody deposition is responsible for tissue damage, the kidneys being one of the main target organs. As the source of pathogenic antibodies, plasma cells are therefore critical players in this harmful scenario, both at systemic and local levels. The aim of the present study was to analyze plasma cells in NZB/W lupus mice and to get a better understanding of the mechanisms underlying their involvement in the renal inflammation process. Using various techniques (i.e. flow cytometry, quantitative PCR, ELISpot), we identified and extensively characterized three plasma cell intermediates, according to their B220/CD138/MHCII expression levels. Each of these cell subsets displays specific proliferation and antibody secretion capacities. Moreover, we evidenced that the inflammation-related CXCR3 chemokine receptor is uniquely expressed by CD138(high)MHCII(+) plasma cells, which encompass both short- and long-lived cells and mostly produce IgG (auto)antibodies. Expression of CXCR3 allows efficient chemotactic responsiveness of these cells to cognate chemokines, which production is up-regulated in the kidneys of diseased NZB/W mice. Finally, using fluorescence and electron microscopy, we demonstrated the presence of CD138(+)CXCR3(+)IgG(+) cells in inflammatory areas in the kidneys, where they are very likely involved in the injury process. Thus, early differentiated CD138(high)MHCII(+) rather than terminally differentiated CD138(high)MHCII(low) plasma cells may be involved in the renal inflammatory injury in lupus, due to CXCR3 expression and IgG secretion.},
keywords = {Animals, Autoantibodies, Cell Differentiation, CXCR3, Dumortier, Gene Expression Regulation, Histocompatibility Antigens Class II, I2CT, Immunoglobulin G, Inbred BALB C, Kidney, Leukocyte Common Antigens, Lupus Nephritis, Mice, Plasma Cells, Receptors, Syndecan-1, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
Humoral responses are central to the development of chronic autoimmune diseases such as systemic lupus erythematosus. Indeed, autoantibody deposition is responsible for tissue damage, the kidneys being one of the main target organs. As the source of pathogenic antibodies, plasma cells are therefore critical players in this harmful scenario, both at systemic and local levels. The aim of the present study was to analyze plasma cells in NZB/W lupus mice and to get a better understanding of the mechanisms underlying their involvement in the renal inflammation process. Using various techniques (i.e. flow cytometry, quantitative PCR, ELISpot), we identified and extensively characterized three plasma cell intermediates, according to their B220/CD138/MHCII expression levels. Each of these cell subsets displays specific proliferation and antibody secretion capacities. Moreover, we evidenced that the inflammation-related CXCR3 chemokine receptor is uniquely expressed by CD138(high)MHCII(+) plasma cells, which encompass both short- and long-lived cells and mostly produce IgG (auto)antibodies. Expression of CXCR3 allows efficient chemotactic responsiveness of these cells to cognate chemokines, which production is up-regulated in the kidneys of diseased NZB/W mice. Finally, using fluorescence and electron microscopy, we demonstrated the presence of CD138(+)CXCR3(+)IgG(+) cells in inflammatory areas in the kidneys, where they are very likely involved in the injury process. Thus, early differentiated CD138(high)MHCII(+) rather than terminally differentiated CD138(high)MHCII(low) plasma cells may be involved in the renal inflammatory injury in lupus, due to CXCR3 expression and IgG secretion.
2012
Thomann Jean-Sébastien, Monneaux Fanny, Creusat Gaëlle, Spanedda Maria Vittoria, Heurtault Béatrice, Habermacher Chloé, Schuber Francis, Bourel-Bonnet Line, Frisch Benoît
Novel glycolipid TLR2 ligands of the type Pam2Cys-α-Gal: synthesis and biological properties Article de journal
Dans: European Journal of Medicinal Chemistry, vol. 51, p. 174–183, 2012, ISSN: 1768-3254.
Résumé | Liens | BibTeX | Étiquettes: Adjuvants, Animals, Cell Line, Chemistry Techniques, Female, Galactose, Glycolipids, Humans, I2CT, Immunologic, ligands, Mice, Monneaux, Structure-Activity Relationship, Synthetic, Team-Dumortier, Toll-Like Receptor 2
@article{thomann_novel_2012,
title = {Novel glycolipid TLR2 ligands of the type Pam2Cys-α-Gal: synthesis and biological properties},
author = {Jean-Sébastien Thomann and Fanny Monneaux and Gaëlle Creusat and Maria Vittoria Spanedda and Béatrice Heurtault and Chloé Habermacher and Francis Schuber and Line Bourel-Bonnet and Benoît Frisch},
doi = {10.1016/j.ejmech.2012.02.039},
issn = {1768-3254},
year = {2012},
date = {2012-05-01},
journal = {European Journal of Medicinal Chemistry},
volume = {51},
pages = {174--183},
abstract = {A more complete understanding of the mechanism of action of TLR agonists has fueled the investigation of new synthetic immunoadjuvants. In this context, we designed and synthesized glycolipids of the type Pam(2)Cys-α-Galactose as novel immunoadjuvants. Their synthesis required modifying a hydrophobic tBoc-[2,3-bispalmitoyloxy-(2R)-propyl]-R-cysteinyl moiety, i.e. the minimal structure required for TLR2 agonist activity, by addition of a hydrophilic head, either an α-Galactosylpyranose or an α-Galactosylfuranose to gain respectively Pam(2)CGalp and Pam(2)CGalf. While preparing a carbohydrate building block, an unexpected stereoselectivity was observed during a halide ion-catalytic process on a protected galactofuranose: the alpha anomer was obtained with surprisingly high selectivity (α/β ratiotextgreater9) and with good isolated yield (51%). The TLR2 binding properties of Pam(2)CGalp and Pam(2)CGalf were then fully evaluated. Their efficiency in triggering the proliferation of BALB/c mouse splenocytes was also compared to that of Pam(2)CAG and Pam(3)CAG, two well-established ligands of TLRs. Moreover, the maturation state of murine dendritic cells previously incubated with either Pam(2)CGalp or Pam(2)CGalf was monitored by flow cytometry and compared to that induced by lipopolysaccharide. Pam(2)CGalp and Pam(2)CGalf were found to be equivalent TLR2 agonists, and induced splenocyte proliferation and DC maturation. With very similar activity, Pam(2)CGalp and Pam(2)CGalf were also 10-fold to 100-fold better than Pam(2)CAG and Pam(3)CAG at inducing B cell proliferation. This represents the first time a glucidic head has been added to the tBoc-[2,3-bispalmitoyloxy-(2R)-propyl]-R-cysteinyl moiety whilst maintaining the immunomodulating activity. This should greatly enrich the data available on Pam(2)C structure/activity relationships.},
keywords = {Adjuvants, Animals, Cell Line, Chemistry Techniques, Female, Galactose, Glycolipids, Humans, I2CT, Immunologic, ligands, Mice, Monneaux, Structure-Activity Relationship, Synthetic, Team-Dumortier, Toll-Like Receptor 2},
pubstate = {published},
tppubtype = {article}
}
A more complete understanding of the mechanism of action of TLR agonists has fueled the investigation of new synthetic immunoadjuvants. In this context, we designed and synthesized glycolipids of the type Pam(2)Cys-α-Galactose as novel immunoadjuvants. Their synthesis required modifying a hydrophobic tBoc-[2,3-bispalmitoyloxy-(2R)-propyl]-R-cysteinyl moiety, i.e. the minimal structure required for TLR2 agonist activity, by addition of a hydrophilic head, either an α-Galactosylpyranose or an α-Galactosylfuranose to gain respectively Pam(2)CGalp and Pam(2)CGalf. While preparing a carbohydrate building block, an unexpected stereoselectivity was observed during a halide ion-catalytic process on a protected galactofuranose: the alpha anomer was obtained with surprisingly high selectivity (α/β ratiotextgreater9) and with good isolated yield (51%). The TLR2 binding properties of Pam(2)CGalp and Pam(2)CGalf were then fully evaluated. Their efficiency in triggering the proliferation of BALB/c mouse splenocytes was also compared to that of Pam(2)CAG and Pam(3)CAG, two well-established ligands of TLRs. Moreover, the maturation state of murine dendritic cells previously incubated with either Pam(2)CGalp or Pam(2)CGalf was monitored by flow cytometry and compared to that induced by lipopolysaccharide. Pam(2)CGalp and Pam(2)CGalf were found to be equivalent TLR2 agonists, and induced splenocyte proliferation and DC maturation. With very similar activity, Pam(2)CGalp and Pam(2)CGalf were also 10-fold to 100-fold better than Pam(2)CAG and Pam(3)CAG at inducing B cell proliferation. This represents the first time a glucidic head has been added to the tBoc-[2,3-bispalmitoyloxy-(2R)-propyl]-R-cysteinyl moiety whilst maintaining the immunomodulating activity. This should greatly enrich the data available on Pam(2)C structure/activity relationships.
Delogu Lucia Gemma, Venturelli Enrica, Manetti Roberto, Pinna Gérard Aimé, Carru Ciriaco, Madeddu Roberto, Murgia Luciano, Sgarrella Francesco, Dumortier Hélène, Bianco Alberto
Ex vivo impact of functionalized carbon nanotubes on human immune cells Article de journal
Dans: Nanomedicine (London, England), vol. 7, no. 2, p. 231–243, 2012, ISSN: 1748-6963.
Résumé | Liens | BibTeX | Étiquettes: carbon, Cells, Cultured, Cytokines, Dumortier, Humans, I2CT, Immunity, Innate, Materials Testing, Nanotubes, T-Lymphocytes, Team-Bianco, Team-Dumortier
@article{delogu_ex_2012,
title = {Ex vivo impact of functionalized carbon nanotubes on human immune cells},
author = {Lucia Gemma Delogu and Enrica Venturelli and Roberto Manetti and Gérard Aimé Pinna and Ciriaco Carru and Roberto Madeddu and Luciano Murgia and Francesco Sgarrella and Hélène Dumortier and Alberto Bianco},
doi = {10.2217/nnm.11.101},
issn = {1748-6963},
year = {2012},
date = {2012-02-01},
journal = {Nanomedicine (London, England)},
volume = {7},
number = {2},
pages = {231--243},
abstract = {AIM: Different studies, carried out by us and others, have investigated the impact of carbon nanotubes (CNTs) in vitro and in animal models. To date, only a few studies have been performed on human cells ex vivo. There is also a lack of comparison between CNTs with varied functionalization and structural properties and their impact on different cell types.
MATERIALS & METHODS: The present ex vivo human study focuses on the impact of a series of functionalized multiwalled CNTs on human T and B lymphocytes, natural killer (NK) cells and monocytes.
RESULTS: Smaller diameter nanotubes are internalized more efficiently. Viability assays displayed the absence of cytotoxicity of all multiwalled CNTs used. Activation assay demonstrated a strong effect on monocytes and NK cells.
CONCLUSION: Our results, on human cells ex vivo, confirmed previous studies demonstrating appropriately functionalized CNTs are nontoxic. The effects on cell functionality were significant for the monocytes and NK cells. These findings encourage the possible use of CNTs for biomedical applications either as carriers of therapeutic molecules or as immune modulator systems.},
keywords = {carbon, Cells, Cultured, Cytokines, Dumortier, Humans, I2CT, Immunity, Innate, Materials Testing, Nanotubes, T-Lymphocytes, Team-Bianco, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
AIM: Different studies, carried out by us and others, have investigated the impact of carbon nanotubes (CNTs) in vitro and in animal models. To date, only a few studies have been performed on human cells ex vivo. There is also a lack of comparison between CNTs with varied functionalization and structural properties and their impact on different cell types.
MATERIALS & METHODS: The present ex vivo human study focuses on the impact of a series of functionalized multiwalled CNTs on human T and B lymphocytes, natural killer (NK) cells and monocytes.
RESULTS: Smaller diameter nanotubes are internalized more efficiently. Viability assays displayed the absence of cytotoxicity of all multiwalled CNTs used. Activation assay demonstrated a strong effect on monocytes and NK cells.
CONCLUSION: Our results, on human cells ex vivo, confirmed previous studies demonstrating appropriately functionalized CNTs are nontoxic. The effects on cell functionality were significant for the monocytes and NK cells. These findings encourage the possible use of CNTs for biomedical applications either as carriers of therapeutic molecules or as immune modulator systems.
MATERIALS & METHODS: The present ex vivo human study focuses on the impact of a series of functionalized multiwalled CNTs on human T and B lymphocytes, natural killer (NK) cells and monocytes.
RESULTS: Smaller diameter nanotubes are internalized more efficiently. Viability assays displayed the absence of cytotoxicity of all multiwalled CNTs used. Activation assay demonstrated a strong effect on monocytes and NK cells.
CONCLUSION: Our results, on human cells ex vivo, confirmed previous studies demonstrating appropriately functionalized CNTs are nontoxic. The effects on cell functionality were significant for the monocytes and NK cells. These findings encourage the possible use of CNTs for biomedical applications either as carriers of therapeutic molecules or as immune modulator systems.
Keravis Thérèse, Monneaux Fanny, Yougbaré Issaka, Gazi Lucien, Bourguignon Jean-Jacques, Muller Sylviane, Lugnier Claire
Disease progression in MRL/lpr lupus-prone mice is reduced by NCS 613, a specific cyclic nucleotide phosphodiesterase type 4 (PDE4) inhibitor Article de journal
Dans: PloS One, vol. 7, no. 1, p. e28899, 2012, ISSN: 1932-6203.
Résumé | Liens | BibTeX | Étiquettes: Adenine, Animals, Cyclic AMP, Cyclic Nucleotide Phosphodiesterases, Disease Progression, Female, Humans, I2CT, Inbred CBA, Inbred MRL lpr, Isoenzymes, Kidney, Lipopolysaccharides, Lupus Erythematosus, Mice, Monneaux, Pentoxifylline, Phosphodiesterase 4 Inhibitors, Proteinuria, Survival Rate, Systemic, Team-Dumortier, Tumor Necrosis Factor-alpha, Type 4, Xanthines
@article{keravis_disease_2012,
title = {Disease progression in MRL/lpr lupus-prone mice is reduced by NCS 613, a specific cyclic nucleotide phosphodiesterase type 4 (PDE4) inhibitor},
author = {Thérèse Keravis and Fanny Monneaux and Issaka Yougbaré and Lucien Gazi and Jean-Jacques Bourguignon and Sylviane Muller and Claire Lugnier},
doi = {10.1371/journal.pone.0028899},
issn = {1932-6203},
year = {2012},
date = {2012-01-01},
journal = {PloS One},
volume = {7},
number = {1},
pages = {e28899},
abstract = {Systemic lupus erythematosus is a polymorphic and multigenic inflammatory autoimmune disease. Cyclic AMP (cAMP) modulates inflammation and the inhibition of cyclic nucleotide phosphodiesterase type 4 (PDE4), which specifically hydrolyzes cAMP, inhibits TNFα secretion. This study was aimed at investigating the evolution of PDE activity and expression levels during the course of the disease in MRL/lpr lupus-prone mice, and to evaluate in these mice the biological and clinical effects of treatments with pentoxifylline, denbufylline and NCS 613 PDE inhibitors. This study reveals that compared to CBA/J control mice, kidney PDE4 activity of MRL/lpr mice increases with the disease progression. Furthermore, it showed that the most potent and selective PDE4 inhibitor NCS 613 is also the most effective molecule in decreasing proteinuria and increasing survival rate of MRL/lpr mice. NCS 613 is a potent inhibitor, which is more selective for the PDE4C subtype (IC₅₀= 1.4 nM) than the other subtypes (PDE4A, IC₅₀= 44 nM; PDE4B, IC₅₀= 48 nM; and PDE4D, IC₅₀= 14 nM). Interestingly, its affinity for the High Affinity Rolipram Binding Site is relatively low (K(i) = 148 nM) in comparison to rolipram (K(i) = 3 nM). Finally, as also observed using MRL/lpr peripheral blood lymphocytes (PBLs), NCS 613 inhibits basal and LPS-induced TNFα secretion from PBLs of lupus patients, suggesting a therapeutic potential of NCS 613 in systemic lupus. This study reveals that PDE4 represent a potential therapeutic target in lupus disease.},
keywords = {Adenine, Animals, Cyclic AMP, Cyclic Nucleotide Phosphodiesterases, Disease Progression, Female, Humans, I2CT, Inbred CBA, Inbred MRL lpr, Isoenzymes, Kidney, Lipopolysaccharides, Lupus Erythematosus, Mice, Monneaux, Pentoxifylline, Phosphodiesterase 4 Inhibitors, Proteinuria, Survival Rate, Systemic, Team-Dumortier, Tumor Necrosis Factor-alpha, Type 4, Xanthines},
pubstate = {published},
tppubtype = {article}
}
Systemic lupus erythematosus is a polymorphic and multigenic inflammatory autoimmune disease. Cyclic AMP (cAMP) modulates inflammation and the inhibition of cyclic nucleotide phosphodiesterase type 4 (PDE4), which specifically hydrolyzes cAMP, inhibits TNFα secretion. This study was aimed at investigating the evolution of PDE activity and expression levels during the course of the disease in MRL/lpr lupus-prone mice, and to evaluate in these mice the biological and clinical effects of treatments with pentoxifylline, denbufylline and NCS 613 PDE inhibitors. This study reveals that compared to CBA/J control mice, kidney PDE4 activity of MRL/lpr mice increases with the disease progression. Furthermore, it showed that the most potent and selective PDE4 inhibitor NCS 613 is also the most effective molecule in decreasing proteinuria and increasing survival rate of MRL/lpr mice. NCS 613 is a potent inhibitor, which is more selective for the PDE4C subtype (IC₅₀= 1.4 nM) than the other subtypes (PDE4A, IC₅₀= 44 nM; PDE4B, IC₅₀= 48 nM; and PDE4D, IC₅₀= 14 nM). Interestingly, its affinity for the High Affinity Rolipram Binding Site is relatively low (K(i) = 148 nM) in comparison to rolipram (K(i) = 3 nM). Finally, as also observed using MRL/lpr peripheral blood lymphocytes (PBLs), NCS 613 inhibits basal and LPS-induced TNFα secretion from PBLs of lupus patients, suggesting a therapeutic potential of NCS 613 in systemic lupus. This study reveals that PDE4 represent a potential therapeutic target in lupus disease.
Lamanna Giuseppe, Russier Julie, Dumortier Hélène, Bianco Alberto
Enhancement of anti-inflammatory drug activity by multivalent adamantane-based dendrons Article de journal
Dans: Biomaterials, vol. 33, no. 22, p. 5610–5617, 2012, ISSN: 1878-5905.
Résumé | Liens | BibTeX | Étiquettes: Animals, Anti-Inflammatory Agents, Cell Line, Cell Survival, Dendrimers, Drug Synergism, Dumortier, I2CT, Ibuprofen, Macrophages, Mice, Team-Bianco, Team-Dumortier
@article{lamanna_enhancement_2012,
title = {Enhancement of anti-inflammatory drug activity by multivalent adamantane-based dendrons},
author = {Giuseppe Lamanna and Julie Russier and Hélène Dumortier and Alberto Bianco},
doi = {10.1016/j.biomaterials.2012.03.072},
issn = {1878-5905},
year = {2012},
date = {2012-01-01},
journal = {Biomaterials},
volume = {33},
number = {22},
pages = {5610--5617},
abstract = {We have developed a straightforward method to prepare 1(st) and 2(nd) generation adamantane-based dendrons, previously called HYDRAmers, bearing at the periphery the anti-inflammatory drug, ibuprofen. The multivalency effect on the drug activity was studied, demonstrating that our multivalent ibuprofen-dendron conjugates exert an enhanced anti-inflammatory activity compared to free ibuprofen, in vitro. These results provide insights into the effect of HYDRAmer multivalency on biological interactions for therapeutic applications.},
keywords = {Animals, Anti-Inflammatory Agents, Cell Line, Cell Survival, Dendrimers, Drug Synergism, Dumortier, I2CT, Ibuprofen, Macrophages, Mice, Team-Bianco, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
We have developed a straightforward method to prepare 1(st) and 2(nd) generation adamantane-based dendrons, previously called HYDRAmers, bearing at the periphery the anti-inflammatory drug, ibuprofen. The multivalency effect on the drug activity was studied, demonstrating that our multivalent ibuprofen-dendron conjugates exert an enhanced anti-inflammatory activity compared to free ibuprofen, in vitro. These results provide insights into the effect of HYDRAmer multivalency on biological interactions for therapeutic applications.
Lacerda Lara, Russier Julie, Pastorin Giorgia, Herrero Antonia M, Venturelli Enrica, Dumortier Hélène, Al-Jamal Khuloud T, Prato Maurizio, Kostarelos Kostas, Bianco Alberto
Translocation mechanisms of chemically functionalised carbon nanotubes across plasma membranes Article de journal
Dans: Biomaterials, vol. 33, no. 11, p. 3334–3343, 2012, ISSN: 1878-5905.
Résumé | Liens | BibTeX | Étiquettes: Animals, carbon, Cell Line, Cell Membrane, Dumortier, I2CT, Macrophages, Mice, Nanotubes, Phagocytosis, Team-Bianco, Team-Dumortier
@article{lacerda_translocation_2012,
title = {Translocation mechanisms of chemically functionalised carbon nanotubes across plasma membranes},
author = {Lara Lacerda and Julie Russier and Giorgia Pastorin and Antonia M Herrero and Enrica Venturelli and Hélène Dumortier and Khuloud T Al-Jamal and Maurizio Prato and Kostas Kostarelos and Alberto Bianco},
doi = {10.1016/j.biomaterials.2012.01.024},
issn = {1878-5905},
year = {2012},
date = {2012-01-01},
journal = {Biomaterials},
volume = {33},
number = {11},
pages = {3334--3343},
abstract = {Understanding the mechanisms responsible for carbon nanotube (CNT) internalisation into live cells is considered critical both from a fundamental point of view and for further engineering of CNT-based delivery systems to intracellular targets. While several studies are focused on the development of such CNT-based delivery systems, attempts to systematically elucidate the cellular uptake mechanisms of CNTs are still rather limited. The aim of the present study is to evaluate the cellular internalisation of chemically functionalised multi-walled carbon nanotubes (f-MWCNTs) in the presence of different well-known cellular uptake inhibitors. Our data reveal how f-MWCNTs are able to translocate across cell membranes of both phagocytic and non-phagocytic cell lines. We have evidenced that at least 30-50% of f-MWCNTs are taken up by cells through an energy-independent mechanism. This characteristic makes nanotubes loaded with therapeutic or diagnostic cargos extremely interesting as the release of active molecules directly into the cytoplasm increase their biological activity and therapeutic efficacy.},
keywords = {Animals, carbon, Cell Line, Cell Membrane, Dumortier, I2CT, Macrophages, Mice, Nanotubes, Phagocytosis, Team-Bianco, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
Understanding the mechanisms responsible for carbon nanotube (CNT) internalisation into live cells is considered critical both from a fundamental point of view and for further engineering of CNT-based delivery systems to intracellular targets. While several studies are focused on the development of such CNT-based delivery systems, attempts to systematically elucidate the cellular uptake mechanisms of CNTs are still rather limited. The aim of the present study is to evaluate the cellular internalisation of chemically functionalised multi-walled carbon nanotubes (f-MWCNTs) in the presence of different well-known cellular uptake inhibitors. Our data reveal how f-MWCNTs are able to translocate across cell membranes of both phagocytic and non-phagocytic cell lines. We have evidenced that at least 30-50% of f-MWCNTs are taken up by cells through an energy-independent mechanism. This characteristic makes nanotubes loaded with therapeutic or diagnostic cargos extremely interesting as the release of active molecules directly into the cytoplasm increase their biological activity and therapeutic efficacy.
2011
Banchet-Cadeddu Aline, Martinez Agathe, Guillarme Stéphane, Parietti Véronique, Monneaux Fanny, Hénon Eric, Renault Jean-Hugues, Nuzillard Jean-Marc, Haudrechy Arnaud
Use of the NEO strategy (Nucleophilic addition/Epoxide Opening) for the synthesis of a new C-galactoside ester analogue of KRN 7000 Article de journal
Dans: Bioorganic & Medicinal Chemistry Letters, vol. 21, no. 8, p. 2510–2514, 2011, ISSN: 1464-3405.
Résumé | Liens | BibTeX | Étiquettes: Animals, Cell Proliferation, Cells, Cultured, Esters, Galactosides, Galactosylceramides, Glycolipids, I2CT, Interferon-gamma, Interleukin-4, Mice, Monneaux, Team-Dumortier
@article{banchet-cadeddu_use_2011,
title = {Use of the NEO strategy (Nucleophilic addition/Epoxide Opening) for the synthesis of a new C-galactoside ester analogue of KRN 7000},
author = {Aline Banchet-Cadeddu and Agathe Martinez and Stéphane Guillarme and Véronique Parietti and Fanny Monneaux and Eric Hénon and Jean-Hugues Renault and Jean-Marc Nuzillard and Arnaud Haudrechy},
doi = {10.1016/j.bmcl.2011.02.044},
issn = {1464-3405},
year = {2011},
date = {2011-04-01},
journal = {Bioorganic & Medicinal Chemistry Letters},
volume = {21},
number = {8},
pages = {2510--2514},
abstract = {Our goal in the search for potentially bioactive analogues of KRN 7000 was to design an easy synthetic approach to a library of analogues using a strategy recently developed in our laboratory based on a Nucleophilic addition followed by an Epoxide Opening (the NEO strategy). Through the use of a common pivotal structure, a new C-galactoside ester analogue (23) was synthesized which showed an encouraging T(H)2 biased response during preliminary biological tests.},
keywords = {Animals, Cell Proliferation, Cells, Cultured, Esters, Galactosides, Galactosylceramides, Glycolipids, I2CT, Interferon-gamma, Interleukin-4, Mice, Monneaux, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
Our goal in the search for potentially bioactive analogues of KRN 7000 was to design an easy synthetic approach to a library of analogues using a strategy recently developed in our laboratory based on a Nucleophilic addition followed by an Epoxide Opening (the NEO strategy). Through the use of a common pivotal structure, a new C-galactoside ester analogue (23) was synthesized which showed an encouraging T(H)2 biased response during preliminary biological tests.
Gaillard Claire, Duval Monique, Dumortier Hélène, Bianco Alberto
Carbon nanotube-coupled cell adhesion peptides are non-immunogenic: a promising step toward new biomedical devices Article de journal
Dans: Journal of Peptide Science: An Official Publication of the European Peptide Society, vol. 17, no. 2, p. 139–142, 2011, ISSN: 1099-1387.
Résumé | Liens | BibTeX | Étiquettes: carbon, Dumortier, Enzyme-Linked Immunosorbent Assay, I2CT, Nanotubes, Peptides, Team-Bianco, Team-Dumortier
@article{gaillard_carbon_2011,
title = {Carbon nanotube-coupled cell adhesion peptides are non-immunogenic: a promising step toward new biomedical devices},
author = {Claire Gaillard and Monique Duval and Hélène Dumortier and Alberto Bianco},
doi = {10.1002/psc.1290},
issn = {1099-1387},
year = {2011},
date = {2011-02-01},
journal = {Journal of Peptide Science: An Official Publication of the European Peptide Society},
volume = {17},
number = {2},
pages = {139--142},
abstract = {Carbon nanotubes functionalized with cell adhesion peptides can be considered as novel, promising candidates for the development of advanced drug delivery systems or for designing new generation of self-assembling nerve 'bridges'. An important step toward the integration of these types of conjugates in living bodies is the assessment of their impact on the immune system. In this direction, an integrin-derived peptide has been covalently conjugated to carbon nanotubes. Following intraperitoneal administration, peptide-carbon nanotubes do not trigger an anti-peptide antibody production. Demonstration of the immune neutrality of peptide-carbon nanotubes reinforces their potential use as substrates for neuronal regeneration in vivo.},
keywords = {carbon, Dumortier, Enzyme-Linked Immunosorbent Assay, I2CT, Nanotubes, Peptides, Team-Bianco, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
Carbon nanotubes functionalized with cell adhesion peptides can be considered as novel, promising candidates for the development of advanced drug delivery systems or for designing new generation of self-assembling nerve 'bridges'. An important step toward the integration of these types of conjugates in living bodies is the assessment of their impact on the immune system. In this direction, an integrin-derived peptide has been covalently conjugated to carbon nanotubes. Following intraperitoneal administration, peptide-carbon nanotubes do not trigger an anti-peptide antibody production. Demonstration of the immune neutrality of peptide-carbon nanotubes reinforces their potential use as substrates for neuronal regeneration in vivo.
Banchet-Cadeddu Aline, Hénon Eric, Dauchez Manuel, Renault Jean-Hugues, Monneaux Fanny, Haudrechy Arnaud
The stimulating adventure of KRN 7000 Article de journal
Dans: Organic & Biomolecular Chemistry, vol. 9, no. 9, p. 3080–3104, 2011, ISSN: 1477-0539.
Résumé | Liens | BibTeX | Étiquettes: Adjuvants, Animals, Antigen, Antigens, CD1d, Galactosylceramides, Helper-Inducer, Humans, I2CT, Immunologic, Monneaux, Receptors, T-Cell, T-Lymphocytes, Team-Dumortier
@article{banchet-cadeddu_stimulating_2011,
title = {The stimulating adventure of KRN 7000},
author = {Aline Banchet-Cadeddu and Eric Hénon and Manuel Dauchez and Jean-Hugues Renault and Fanny Monneaux and Arnaud Haudrechy},
doi = {10.1039/c0ob00975j},
issn = {1477-0539},
year = {2011},
date = {2011-01-01},
journal = {Organic & Biomolecular Chemistry},
volume = {9},
number = {9},
pages = {3080--3104},
abstract = {Associated with the CD1d protein, KRN 7000, a potent synthetic α-galactosylceramide, is known to activate the invariant NKT immune cells. This stimulation then leads to the production of different cytokines modulating a T(H)1/T(H)2 immune response balance involved in protection against several pathologies such as autoimmune diseases and cancers. Various efforts have been made toward the synthesis of simple and more functionalized analogues in order to selectively induce T(H)1 or T(H)2-type cytokine production. Since the discovery of KRN 7000, structure-activity relationships, crystallographic and modelling studies have pointed to the potential of several GalCer analogues in term of selective bioactivity, and have highlighted interesting elements in order to better understand the recognition and activation mechanisms of immune iNKT cells. By presenting an up-to-date library of analogues, collecting recent breakthroughs done in crystallography and molecular modelling, and relating them to the available biological results, we hope that this review will highlight and help the scientific community in their KRN research.},
keywords = {Adjuvants, Animals, Antigen, Antigens, CD1d, Galactosylceramides, Helper-Inducer, Humans, I2CT, Immunologic, Monneaux, Receptors, T-Cell, T-Lymphocytes, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
Associated with the CD1d protein, KRN 7000, a potent synthetic α-galactosylceramide, is known to activate the invariant NKT immune cells. This stimulation then leads to the production of different cytokines modulating a T(H)1/T(H)2 immune response balance involved in protection against several pathologies such as autoimmune diseases and cancers. Various efforts have been made toward the synthesis of simple and more functionalized analogues in order to selectively induce T(H)1 or T(H)2-type cytokine production. Since the discovery of KRN 7000, structure-activity relationships, crystallographic and modelling studies have pointed to the potential of several GalCer analogues in term of selective bioactivity, and have highlighted interesting elements in order to better understand the recognition and activation mechanisms of immune iNKT cells. By presenting an up-to-date library of analogues, collecting recent breakthroughs done in crystallography and molecular modelling, and relating them to the available biological results, we hope that this review will highlight and help the scientific community in their KRN research.
2010
Lacotte Stéphanie, Dumortier Hélène, Décossas Marion, Briand Jean-Paul, Muller Sylviane
Identification of new pathogenic players in lupus: autoantibody-secreting cells are present in nephritic kidneys of (NZBxNZW)F1 mice Article de journal
Dans: Journal of Immunology (Baltimore, Md.: 1950), vol. 184, no. 7, p. 3937–3945, 2010, ISSN: 1550-6606.
Résumé | Liens | BibTeX | Étiquettes: Animals, Autoantibodies, Autoantigens, B-Lymphocytes, Dumortier, Enzyme-Linked Immunosorbent Assay, Female, Histones, I2CT, Immunoblotting, Immunohistochemistry, Inbred BALB C, Inbred NZB, Lupus Nephritis, Mice, Team-Dumortier
@article{lacotte_identification_2010,
title = {Identification of new pathogenic players in lupus: autoantibody-secreting cells are present in nephritic kidneys of (NZBxNZW)F1 mice},
author = {Stéphanie Lacotte and Hélène Dumortier and Marion Décossas and Jean-Paul Briand and Sylviane Muller},
doi = {10.4049/jimmunol.0902595},
issn = {1550-6606},
year = {2010},
date = {2010-04-01},
journal = {Journal of Immunology (Baltimore, Md.: 1950)},
volume = {184},
number = {7},
pages = {3937--3945},
abstract = {An important hallmark of systemic lupus erythematosus is the production of autoantibodies specific for nuclear Ags, among which nucleosomes and their constituents, DNA and histones. It is widely admitted that some of these autoantibodies contribute largely in lupus pathogenesis because of their nephritogenic potential. However, the underlying mechanisms are still debated. In this study, we analyzed the autoimmune response against histone H2B during the course of the disease in lupus-prone (NZBxNZW)F1 mice, both in lymphoid organs and kidneys, and we assessed its potential involvement in lupus pathogenicity. We found that the N-terminal region of histone H2B represents a preferential target for circulating autoantibodies, which kinetics of appearance positively correlates with disease development. Furthermore, immunization of preautoimmune (NZBxNZW)F1 mice with H2B peptide 1-25 accelerates the disease. Kidney eluates from diseased (NZBxNZW)F1 mice do contain IgG Abs reacting with this peptide, and this H2B sequence was found to be accessible to specific Ab probes in Ag-containing deposits detected in nephritic kidneys. Finally, compared with control normal mice and to young preautoimmune (NZBxNZW)F1 animals, the frequency of cells secreting autoantibodies reacting with peptide 1-25 was significantly raised in the spleen and bone marrow and most importantly on a pathophysiological point of view, locally, in nephritic kidneys of diseased (NZBxNZW)F1 mice. Altogether our results demonstrate the existence in (NZBxNZW)F1 mice of both a systemic and local B cell response targeting the N-terminal region of histone H2B, and highlight the potential implication of this nuclear domain in lupus pathology.},
keywords = {Animals, Autoantibodies, Autoantigens, B-Lymphocytes, Dumortier, Enzyme-Linked Immunosorbent Assay, Female, Histones, I2CT, Immunoblotting, Immunohistochemistry, Inbred BALB C, Inbred NZB, Lupus Nephritis, Mice, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
An important hallmark of systemic lupus erythematosus is the production of autoantibodies specific for nuclear Ags, among which nucleosomes and their constituents, DNA and histones. It is widely admitted that some of these autoantibodies contribute largely in lupus pathogenesis because of their nephritogenic potential. However, the underlying mechanisms are still debated. In this study, we analyzed the autoimmune response against histone H2B during the course of the disease in lupus-prone (NZBxNZW)F1 mice, both in lymphoid organs and kidneys, and we assessed its potential involvement in lupus pathogenicity. We found that the N-terminal region of histone H2B represents a preferential target for circulating autoantibodies, which kinetics of appearance positively correlates with disease development. Furthermore, immunization of preautoimmune (NZBxNZW)F1 mice with H2B peptide 1-25 accelerates the disease. Kidney eluates from diseased (NZBxNZW)F1 mice do contain IgG Abs reacting with this peptide, and this H2B sequence was found to be accessible to specific Ab probes in Ag-containing deposits detected in nephritic kidneys. Finally, compared with control normal mice and to young preautoimmune (NZBxNZW)F1 animals, the frequency of cells secreting autoantibodies reacting with peptide 1-25 was significantly raised in the spleen and bone marrow and most importantly on a pathophysiological point of view, locally, in nephritic kidneys of diseased (NZBxNZW)F1 mice. Altogether our results demonstrate the existence in (NZBxNZW)F1 mice of both a systemic and local B cell response targeting the N-terminal region of histone H2B, and highlight the potential implication of this nuclear domain in lupus pathology.
Parietti Véronique, Chifflot Hélène, Sibilia Jean, Muller Sylviane, Monneaux Fanny
Rituximab treatment overcomes reduction of regulatory iNKT cells in patients with rheumatoid arthritis Article de journal
Dans: Clinical Immunology (Orlando, Fla.), vol. 134, no. 3, p. 331–339, 2010, ISSN: 1521-7035.
Résumé | Liens | BibTeX | Étiquettes: Adult, Age Factors, Aged, Antibodies, Antirheumatic Agents, arthritis, Female, Flow Cytometry, Humans, I2CT, Longitudinal Studies, Male, Middle Aged, Monneaux, Monoclonal, Murine-Derived, Natural Killer T-Cells, Nonparametric, rheumatoid, Rituximab, Sex Factors, Statistics, Team-Dumortier, Young Adult
@article{parietti_rituximab_2010,
title = {Rituximab treatment overcomes reduction of regulatory iNKT cells in patients with rheumatoid arthritis},
author = {Véronique Parietti and Hélène Chifflot and Jean Sibilia and Sylviane Muller and Fanny Monneaux},
doi = {10.1016/j.clim.2009.11.007},
issn = {1521-7035},
year = {2010},
date = {2010-01-01},
journal = {Clinical Immunology (Orlando, Fla.)},
volume = {134},
number = {3},
pages = {331--339},
abstract = {Invariant natural killer T (iNKT) cells are a subset of T cells that recognize glycolipid antigens presented by the CD1d molecule. Accumulating evidences showed that iNKT cells are implicated in the regulatory mechanisms that control autoimmunity. We evaluated the number of circulating iNKT cells in patients with rheumatoid arthritis (RA) by flow cytometry and performed a longitudinal analysis of iNKT cell frequency in RA patients who were given an anti-CD20 therapy. Significantly lower iNKT cell numbers were measured in the blood from RA patients compared to healthy individuals (ptextless0.0001) and low iNKT cell frequencies were rather associated with an active disease. In RA patients who received rituximab treatment, iNKT cell number was increased in relation to the clinical outcome. We demonstrated that the number of iNKT cells is altered in RA patients and that following rituximab therapy, clinical remission of RA is associated with an increase of iNKT cell frequency.},
keywords = {Adult, Age Factors, Aged, Antibodies, Antirheumatic Agents, arthritis, Female, Flow Cytometry, Humans, I2CT, Longitudinal Studies, Male, Middle Aged, Monneaux, Monoclonal, Murine-Derived, Natural Killer T-Cells, Nonparametric, rheumatoid, Rituximab, Sex Factors, Statistics, Team-Dumortier, Young Adult},
pubstate = {published},
tppubtype = {article}
}
Invariant natural killer T (iNKT) cells are a subset of T cells that recognize glycolipid antigens presented by the CD1d molecule. Accumulating evidences showed that iNKT cells are implicated in the regulatory mechanisms that control autoimmunity. We evaluated the number of circulating iNKT cells in patients with rheumatoid arthritis (RA) by flow cytometry and performed a longitudinal analysis of iNKT cell frequency in RA patients who were given an anti-CD20 therapy. Significantly lower iNKT cell numbers were measured in the blood from RA patients compared to healthy individuals (ptextless0.0001) and low iNKT cell frequencies were rather associated with an active disease. In RA patients who received rituximab treatment, iNKT cell number was increased in relation to the clinical outcome. We demonstrated that the number of iNKT cells is altered in RA patients and that following rituximab therapy, clinical remission of RA is associated with an increase of iNKT cell frequency.
2009
Chamouard Patrick, Monneaux Fanny, Richert Zoe, Voegeli Anne-Claire, Lavaux Thomas, Gaub Marie Pierre, Baumann René, Oudet Pierre, Muller Sylviane
Diminution of Circulating CD4+CD25 high Ŧ cells in naïve Crohn's disease Article de journal
Dans: Digestive Diseases and Sciences, vol. 54, no. 10, p. 2084–2093, 2009, ISSN: 1573-2568.
Résumé | Liens | BibTeX | Étiquettes: Adult, Aged, Blood Cell Count, CD4 Antigens, Colitis, Crohn Disease, Female, Flow Cytometry, Humans, I2CT, Interleukin-2 Receptor alpha Subunit, Lymphocyte Subsets, Male, Middle Aged, Monneaux, Regulatory, T-Lymphocytes, Team-Dumortier, Ulcerative
@article{chamouard_diminution_2009,
title = {Diminution of Circulating CD4+CD25 high Ŧ cells in naïve Crohn's disease},
author = {Patrick Chamouard and Fanny Monneaux and Zoe Richert and Anne-Claire Voegeli and Thomas Lavaux and Marie Pierre Gaub and René Baumann and Pierre Oudet and Sylviane Muller},
doi = {10.1007/s10620-008-0590-6},
issn = {1573-2568},
year = {2009},
date = {2009-10-01},
journal = {Digestive Diseases and Sciences},
volume = {54},
number = {10},
pages = {2084--2093},
abstract = {Crohn's disease is considered to be caused either by an excess of T-cell effector functions and/or by a defective regulatory T-cell compartment. The aim of this study was to assess in Crohn's disease the frequency of circulating CD4(+)CD25(high) T cells that possess regulatory T-cell functions and CD4(+)CD25(low) T cells that contain activated T cells. Flow cytometry of peripheral blood was used to assess CD4(+)CD25(high) and CD4(+)CD25(low) T-cell frequencies in a cohort of 66 patients with Crohn's disease in comparison to 19 patients with ulcerative colitis and 31 healthy individuals enrolled as controls. The CD4(+)CD25(high) T-cell frequency was significantly lowered in naïve Crohn's disease (P = 0.013) and in ulcerative colitis (P = 0.001). CD4(+)CD25(low) T-cell frequency was increased in Crohn's disease (P = 0.0001) and in ulcerative colitis (P = 0.0002). Both CD4(+)CD25(high) and CD4(+)CD25(low) T-cell frequencies are altered in naïve Crohn's disease resulting in an imbalance between both populations and a relative contraction of the CD4(+)CD25(high) T-cell population.},
keywords = {Adult, Aged, Blood Cell Count, CD4 Antigens, Colitis, Crohn Disease, Female, Flow Cytometry, Humans, I2CT, Interleukin-2 Receptor alpha Subunit, Lymphocyte Subsets, Male, Middle Aged, Mon