title: Cyclosporin A inhibits the production of IL-17 by memory Th17 cells from healthy individuals and patients with rheumatoid arthritis.
abstract: Recent evidence from several studies indicated that IL-17-producing Th17 cells can represent the key effector cells in the induction and development of autoimmune disorders. Cyclosporine A (CsA) is a commonly used immunosuppressant to treat lots of autoimmune diseases including rheumatoid arthritis (RA). Here, we demonstrated that PBMCs and purified CD4(+) T cells from healthy individuals and patients with RA could be induced to produce large amounts of IL-17 after stimulation with anti-CD3 plus anti-CD28 mAbs. Phenotypic analysis indicated that the majority of IL-17-producing cells were Th17 cells with memory phenotype. The addition of CsA into cell cultures significantly inhibited the IL-17 production by Th17 cells at protein and at mRNA levels. Compared to the PBMCs from normal individuals, PBMCs from the patients with RA produced higher levels of IL-17 that was also significantly inhibited by CsA both at protein and at mRNA levels. The mechanism might be the effect of CsA on the T cells activation because the expression of CD69 and CD25 molecules on T cells was markedly reduced in the presence of CsA. Taken together, these results demonstrated that CsA suppressed the IL-17 production and inhibited the Th17 cells differentiation from both healthy individuals and patients with RA.
authors.affiliation: Department of Immunology, Zhongshan School of Medicine, State Ministry of Education Key Laboratory of Tropical Diseases Control Research, Sun Yat-sen University, #74 Zhong-shan 2nd Road, Guangzhou, Guangdong Province 510080, China.
authors.forename: Cai
authors.initials: C
authors.lastname: Zhang
authors.forename: Jianyuan
authors.initials: J
authors.lastname: Zhang
authors.forename: Binyan
authors.initials: B
authors.lastname: Yang
authors.forename: Changyou
authors.initials: C
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007156:Immunologic Memory; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D037181:Lectins, C-Type; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000187:drug effects*; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects*; D013997:Time Factors; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016572:Cyclosporine; D007166:Immunosuppressive Agents; D007371:Interferon-gamma; D020381:Interleukin-17; D053645:Interleukin-2 Receptor alpha Subunit; D037181:Lectins, C-Type; D012333:RNA, Messenger; D000099192:CD69 Antigens