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	Xiaoyin Niu, Dongyi He, Xin Zhang, Tao Yue, Ningli Li, Jingwu Z Zhang, Chen Dong, Guangjie Chen
Journal	Human immunology (Hum Immunol) Vol. 71 Issue 4 Pg. 334-41 (Apr 2010) ISSN: 1879-1166 [Electronic] United States
PMID	20079789 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	CD4 Antigens FOXP3 protein, human Forkhead Transcription Factors Interleukin-17 Interleukins Nuclear Receptor Subfamily 1, Group F, Member 3 RORC protein, human interleukin-21
Topics	Adult Aged Animals Arthritis, Rheumatoid (blood, immunology, pathology) CD4 Antigens (biosynthesis) Cell Proliferation (drug effects) Cells, Cultured Female Forkhead Transcription Factors (genetics, metabolism) Gene Expression Regulation (drug effects, immunology) Humans Interleukin-17 (metabolism) Interleukins (immunology, pharmacology) Male Mice Middle Aged Nuclear Receptor Subfamily 1, Group F, Member 3 (genetics, immunology, metabolism) Synovial Membrane (pathology) T-Lymphocyte Subsets (drug effects, immunology, metabolism, pathology) T-Lymphocytes (drug effects, immunology, metabolism, pathology)

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