Publications
2017
Nehmar Ramzi, Alsaleh Ghada, Voisin Benjamin, Flacher Vincent, Mariotte Alexandre, Saferding Victoria, Puchner Antonia, Niederreiter Birgit, Vandamme Thierry, Schabbauer Gernot, Kastner Philippe, Chan Susan, Kirstetter Peggy, Holcmann Martin, Mueller Christopher, Sibilia Jean, Bahram Seiamak, Blüml Stephan, Georgel Philippe
Therapeutic Modulation of Plasmacytoid Dendritic Cells in Experimental Arthritis Article de journal
Dans: Arthritis & Rheumatology (Hoboken, N.J.), vol. 69, no. 11, p. 2124–2135, 2017, ISSN: 2326-5205.
Résumé | Liens | BibTeX | Étiquettes: Activation, Adjuvants, Aminoquinolines, Analysis, Animal, Animals, arthritis, Assay, cancer, Cells, cytokine, Cytokines, Dendritic Cells, DEPLETION, Disease Models, drug effects, Enzyme-Linked Immunosorbent Assay, Experimental, Flow Cytometry, Gene Expression Profiling, Genetics, GLYCOPROTEIN, Glycoproteins, Human, Humans, IFN, IKAROS, Ikaros Transcription Factor, imiquimod, Immunologic, Immunology, immunopathology, inflammation, interferon, Interferon Type I, interferons, Knockout, Membrane, Membrane Glycoproteins, METHOD, methods, Mice, MODULATION, mouse, Necrosis, NECROSIS-FACTOR-ALPHA, pathogenesis, Patients, Pharmacology, physiology, plasmacytoid dendritic cells, Protein, Receptor, Reverse Transcriptase Polymerase Chain Reaction, rheumatoid, rheumatoid arthritis, Serum, signaling, Team-Mueller, TLR7, Toll-Like Receptor 7, TOPICAL APPLICATION, Transcription, TRANSCRIPTION FACTOR, transcriptome, transgenic, tumor, Tumor Necrosis Factor, Tumor Necrosis Factor-alpha
@article{nehmar_therapeutic_2017,
title = {Therapeutic Modulation of Plasmacytoid Dendritic Cells in Experimental Arthritis},
author = {Ramzi Nehmar and Ghada Alsaleh and Benjamin Voisin and Vincent Flacher and Alexandre Mariotte and Victoria Saferding and Antonia Puchner and Birgit Niederreiter and Thierry Vandamme and Gernot Schabbauer and Philippe Kastner and Susan Chan and Peggy Kirstetter and Martin Holcmann and Christopher Mueller and Jean Sibilia and Seiamak Bahram and Stephan Blüml and Philippe Georgel},
doi = {10.1002/art.40225},
issn = {2326-5205},
year = {2017},
date = {2017-01-01},
journal = {Arthritis & Rheumatology (Hoboken, N.J.)},
volume = {69},
number = {11},
pages = {2124--2135},
abstract = {OBJECTIVE: The role of plasmacytoid dendritic cells (PDCs) and type I interferons (IFNs) in rheumatoid arthritis (RA) remains a subject of controversy. This study was undertaken to explore the contribution of PDCs and type I IFNs to RA pathogenesis using various animal models of PDC depletion and to monitor the effect of localized PDC recruitment and activation on joint inflammation and bone damage.
METHODS: Mice with K/BxN serum-induced arthritis, collagen-induced arthritis, and human tumor necrosis factor transgene insertion were studied. Symptoms were evaluated by visual scoring, quantification of paw swelling, determination of cytokine levels by enzyme-linked immunosorbent assay, and histologic analysis. Imiquimod-dependent therapeutic effects were monitored by transcriptome analysis (using quantitative reverse transcriptase-polymerase chain reaction) and flow cytometric analysis of the periarticular tissue.
RESULTS: PDC-deficient mice showed exacerbation of inflammatory and arthritis symptoms after arthritogenic serum transfer. In contrast, enhancing PDC recruitment and activation to arthritic joints by topical application of the Toll-like receptor 7 (TLR-7) agonist imiquimod significantly ameliorated arthritis in various mouse models. Imiquimod induced an IFN signature and led to reduced infiltration of inflammatory cells.
CONCLUSION: The therapeutic effects of imiquimod on joint inflammation and bone destruction are dependent on TLR-7 sensing by PDCs and type I IFN signaling. Our findings indicate that local recruitment and activation of PDCs represents an attractive therapeutic opportunity for RA patients.},
keywords = {Activation, Adjuvants, Aminoquinolines, Analysis, Animal, Animals, arthritis, Assay, cancer, Cells, cytokine, Cytokines, Dendritic Cells, DEPLETION, Disease Models, drug effects, Enzyme-Linked Immunosorbent Assay, Experimental, Flow Cytometry, Gene Expression Profiling, Genetics, GLYCOPROTEIN, Glycoproteins, Human, Humans, IFN, IKAROS, Ikaros Transcription Factor, imiquimod, Immunologic, Immunology, immunopathology, inflammation, interferon, Interferon Type I, interferons, Knockout, Membrane, Membrane Glycoproteins, METHOD, methods, Mice, MODULATION, mouse, Necrosis, NECROSIS-FACTOR-ALPHA, pathogenesis, Patients, Pharmacology, physiology, plasmacytoid dendritic cells, Protein, Receptor, Reverse Transcriptase Polymerase Chain Reaction, rheumatoid, rheumatoid arthritis, Serum, signaling, Team-Mueller, TLR7, Toll-Like Receptor 7, TOPICAL APPLICATION, Transcription, TRANSCRIPTION FACTOR, transcriptome, transgenic, tumor, Tumor Necrosis Factor, Tumor Necrosis Factor-alpha},
pubstate = {published},
tppubtype = {article}
}
METHODS: Mice with K/BxN serum-induced arthritis, collagen-induced arthritis, and human tumor necrosis factor transgene insertion were studied. Symptoms were evaluated by visual scoring, quantification of paw swelling, determination of cytokine levels by enzyme-linked immunosorbent assay, and histologic analysis. Imiquimod-dependent therapeutic effects were monitored by transcriptome analysis (using quantitative reverse transcriptase-polymerase chain reaction) and flow cytometric analysis of the periarticular tissue.
RESULTS: PDC-deficient mice showed exacerbation of inflammatory and arthritis symptoms after arthritogenic serum transfer. In contrast, enhancing PDC recruitment and activation to arthritic joints by topical application of the Toll-like receptor 7 (TLR-7) agonist imiquimod significantly ameliorated arthritis in various mouse models. Imiquimod induced an IFN signature and led to reduced infiltration of inflammatory cells.
CONCLUSION: The therapeutic effects of imiquimod on joint inflammation and bone destruction are dependent on TLR-7 sensing by PDCs and type I IFN signaling. Our findings indicate that local recruitment and activation of PDCs represents an attractive therapeutic opportunity for RA patients.
2010
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}
}
2009
Lacotte Stéphanie, Brun Susana, Muller Sylviane, Dumortier Hélène
CXCR3, inflammation, and autoimmune diseases Article de journal
Dans: Annals of the New York Academy of Sciences, vol. 1173, p. 310–317, 2009, ISSN: 1749-6632.
Résumé | Liens | BibTeX | Étiquettes: Animals, arthritis, Biological, Chemokine CXCL10, Chemokine CXCL11, Chemokine CXCL9, CXCR3, Dumortier, Humans, I2CT, inflammation, Lupus Erythematosus, Models, Receptors, rheumatoid, Systemic, Team-Dumortier
@article{lacotte_cxcr3_2009,
title = {CXCR3, inflammation, and autoimmune diseases},
author = {Stéphanie Lacotte and Susana Brun and Sylviane Muller and Hélène Dumortier},
doi = {10.1111/j.1749-6632.2009.04813.x},
issn = {1749-6632},
year = {2009},
date = {2009-01-01},
journal = {Annals of the New York Academy of Sciences},
volume = {1173},
pages = {310--317},
abstract = {CXCR3 is a G protein-coupled, seven-transmembrane receptor that binds and is activated by the three IFN-gamma-inducible chemokines of the CXC family named CXCL9, CXCL10, and CXCL11. These chemokines are not constitutively expressed but are up-regulated in a proinflammatory cytokine milieu. Consequently, their major function is to selectively recruit immune cells at inflammation sites, but they also play a role in angiogenesis mechanisms. In the last few years, strong experimental and clinical evidence has been obtained supporting the idea that the CXCR3 pathway is involved in the development of autoimmune diseases, especially by creating local amplification loops of inflammation in target organs, thereby inducing worsening of clinical manifestations. This article briefly reviews what we know today about the nature and functions of CXCR3, with special emphasis on its involvement in two main rheumatic systemic autoimmune diseases, namely rheumatoid arthritis and systemic lupus erythematosus.},
keywords = {Animals, arthritis, Biological, Chemokine CXCL10, Chemokine CXCL11, Chemokine CXCL9, CXCR3, Dumortier, Humans, I2CT, inflammation, Lupus Erythematosus, Models, Receptors, rheumatoid, Systemic, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
2005
Hayer Silvia, Tohidast-Akrad Makiyeh, Haralambous Silva, Jahn-Schmid Beatrice, Skriner Karl, Trembleau Sylvie, Dumortier Hélène, Pinol-Roma Serafin, Redlich Kurt, Schett Georg, Muller Sylviane, Kollias George, Smolen Josef, Steiner Günter
Dans: Journal of Immunology (Baltimore, Md.: 1950), vol. 175, no. 12, p. 8327–8336, 2005, ISSN: 0022-1767.
Résumé | Liens | BibTeX | Étiquettes: Animals, Antibody Formation, arthritis, Autoantibodies, Autoantigens, Dumortier, Gene Expression Regulation, Heterogeneous-Nuclear Ribonucleoprotein Group A-B, Humans, I2CT, Joints, Mice, rheumatoid, Team-Dumortier, Tissue Distribution, transgenic, Tumor Necrosis Factor-alpha
@article{hayer_aberrant_2005,
title = {Aberrant expression of the autoantigen heterogeneous nuclear ribonucleoprotein-A2 (RA33) and spontaneous formation of rheumatoid arthritis-associated anti-RA33 autoantibodies in TNF-alpha transgenic mice},
author = {Silvia Hayer and Makiyeh Tohidast-Akrad and Silva Haralambous and Beatrice Jahn-Schmid and Karl Skriner and Sylvie Trembleau and Hélène Dumortier and Serafin Pinol-Roma and Kurt Redlich and Georg Schett and Sylviane Muller and George Kollias and Josef Smolen and Günter Steiner},
doi = {10.4049/jimmunol.175.12.8327},
issn = {0022-1767},
year = {2005},
date = {2005-12-01},
journal = {Journal of Immunology (Baltimore, Md.: 1950)},
volume = {175},
number = {12},
pages = {8327--8336},
abstract = {Human TNF-alpha transgenic (hTNFtg) mice develop erosive arthritis closely resembling rheumatoid arthritis (RA). To investigate mechanisms leading to pathological autoimmune reactions in RA, we examined hTNFtg animals for the presence of RA-associated autoantibodies including Abs to citrullinated epitopes (anti-cyclic citrullinated peptide), heterogeneous nuclear ribonucleoprotein (hnRNP)-A2 (anti-RA33), and heat shock proteins (hsp) (anti-hsp). Although IgM anti-hsp Abs were detected in 40% of hTNFtg and control mice, IgG anti-hsp Abs were rarely seen, and anti-cyclic citrullinated peptide Abs were not seen at all. In contrast, textgreater50% of hTNFtg mice showed IgG anti-RA33 autoantibodies, which became detectable shortly after the onset of arthritis. These Abs were predominantly directed to a short epitope, which was identical with an epitope previously described in MRL/lpr mice. Incidence of anti-RA33 was significantly decreased in mice treated with the osteoclast inhibitor osteoprotegerin and also in c-fos-deficient mice lacking osteoclasts. Pronounced expression of hnRNP-A2 and a smaller splice variant was seen in joints of hTNFtg mice, whereas expression was low in control animals. Although the closely related hnRNP-A1 was also overexpressed, autoantibodies to this protein were infrequently detected. Because expression of hnRNP-A2 in thymus, spleen, brain, and lung was similar in hTNFtg and control mice, aberrant expression appeared to be restricted to the inflamed joint. Finally, immunization of hTNFtg mice with recombinant hnRNP-A2 or a peptide harboring the major B cell epitope aggravated arthritis. These findings suggest that overproduction of TNF-alpha leads to aberrant expression of hnRNP-A2 in the rheumatoid joint and subsequently to autoimmune reactions, which may enhance the inflammatory and destructive process.},
keywords = {Animals, Antibody Formation, arthritis, Autoantibodies, Autoantigens, Dumortier, Gene Expression Regulation, Heterogeneous-Nuclear Ribonucleoprotein Group A-B, Humans, I2CT, Joints, Mice, rheumatoid, Team-Dumortier, Tissue Distribution, transgenic, Tumor Necrosis Factor-alpha},
pubstate = {published},
tppubtype = {article}
}