title: IL-21 regulates Th17 cells in rheumatoid arthritis.
abstract: IL-21 is a type I cytokine that like IL-2, IL-4, IL-7, IL-9, and IL-15 uses the common gamma chain of cytokine receptor. IL-21 has been shown to regulate the function of T cells, B cells, natural killer cells, and dendritic cells in immune responses. Although activated CD4(+) T cells produce IL-21, recent data suggest that novel subsets of effector T cells are the major producers in immune responses. In this study, we show that IL-21 expression correlates with the presence of Th17 cells in synovial fluid (SF) and peripheral blood in rheumatoid arthritis patients. Human CCR6+ CD4(+) T cells produce high levels of both IL-21 and IL-17. Similar to mouse T cells, IL-21 auto-regulates its own production in human CD4(+) T cells. IL-21 potently enhances Th17 proliferation and suppresses Foxp3 expression, leading to the expression of RORC. IL-21 is therefore an autocrine cytokine that regulates human Th17 cells in rheumatoid arthritis, and serves as a good target for treating this autoimmune disease.
authors.affiliation: Department of Immunology, Shanghai institute of Immunology, Shanghai, People's Republic of China.
authors.forename: Xiaoyin
authors.initials: X
authors.lastname: Niu
authors.forename: Dongyi
authors.initials: D
authors.lastname: He
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Tao
authors.initials: T
authors.lastname: Yue
authors.forename: Ningli
authors.initials: N
authors.lastname: Li
authors.forename: Jingwu Z
authors.initials: JZ
authors.lastname: Zhang
authors.forename: Chen
authors.initials: C
authors.lastname: Dong
authors.forename: Guangjie
authors.initials: G
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology* / Q000473:pathology; D015704:CD4 Antigens / Q000096:biosynthesis; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism; D007378:Interleukins / Q000276:immunology / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013583:Synovial Membrane / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000098546:Interleukin-21
chemical_list: D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D020381:Interleukin-17; D007378:Interleukins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539900:RORC protein, human; D000098546:Interleukin-21