1. Interleukin-6 Receptor Blockade Enhances CD39+ Regulatory T Cell Development in Rheumatoid Arthritis and in Experimental Arthritis
- Author
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Thiolat, A., Semerano, L., Pers, Y., Biton, J., Lemeiter, D., Portales, P., Quentin, J., Jorgensen, C., Decker, P., Boissier, M.-C., Louis-Plence, P., Bessis, N., Physiopathologie, Cibles et Thérapies de la Polyarthrite Rhumatoïde, Université Sorbonne Paris Nord-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris 13, Sorbonne Paris Cité , BPC, Department of Rheumatology, Hôpital Avicenne, APHP, INSERM UMR 1125, Paris 13 University, Bobigny, Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Lapeyronie [Montpellier] (CHU), Hôpital Saint Eloi, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules souches mésenchymateuses, environnement articulaire et immunothérapies de la polyarthrite rhumatoide, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR3, Université Montpellier 1 (UM1)-Université Montpellier 1 (UM1), Unrestricted grants were provided by Roche and Chugai Pharma France. These companies had no role in the study design or in the collection, analysis, or interpretation of the data, the writing of the manuscript, or the decision to submit the manuscript for publication. Publication of this article was not contingent upon approval by Roche and Chugai Pharma France., Université Montpellier 1 (UM1)-IFR3, and Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)
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[SDV]Life Sciences [q-bio] ,chemical and pharmacologic phenomena ,hemic and immune systems - Abstract
International audience; ObjectiveThe rationale for blocking interleukin‐6 (IL‐6) in rheumatoid arthritis (RA) lies chiefly in the proinflammatory effect of this cytokine. Few studies have evaluated the consequences of anti–IL‐6 receptor (IL‐6R) antibody treatment on Treg cells. This study was undertaken to elucidate the mechanism of action of anti–IL‐6R antibody treatment by studying the effects on Treg cells in an experimental arthritis model and in patients with RA.MethodsMice with collagen‐induced arthritis (CIA) were treated with a mouse anti–IL‐6R antibody (MR16‐1), and changes in Treg, Th1, and Th17 cells were assessed at key time points during the course of the disease. Peripheral blood from 15 RA patients was collected on day 0 and after 3 months of tocilizumab treatment for flow cytometry analysis of Th17 and Treg cells.ResultsIn MR16‐1–treated mice, Th17 cell frequencies were unchanged, whereas Treg cell frequencies were increased. The Treg cell phenotype showed marked changes, with an increase in the frequency of CD39+ Treg cells in the lymph nodes and spleen. Interestingly, similar CD39+ Treg cell expansion was observed in RA patients who were tocilizumab responders at 3 months, with no change in Th17 cell frequency. Moreover, fluorescence‐activated cell–sorted CD39+ Treg cells from responder RA patients were functionally able to suppress the proliferation of conventional T cells.ConclusionIn both CIA and RA, the frequency of functionally suppressive CD39+ Treg cells is increased as a result of anti–IL‐6R treatment, whereas Th17 cells are unaffected. The modification of Treg cell frequency and phenotype may be one of the mechanisms involved in the therapeutic effect of IL‐6 blockade in RA.
- Published
- 2014