Pathogenic conversion of Foxp3⁺ T cells into T_H17 cells in autoimmune arthritis

Noriko Komatsu, Kazuo Okamato, Shinichiro Sawa, Tomoki Nakashima, Masatsugu Oh-hora, Tatsuhiko Kodama, Sakae Tanaka, Jeffrey A Bluestone, and Hiroshi Takayanagi.

Nature medicine. (2014) January,1, volume 20, 62-70.

Speaker: Yun-Chiao Ding (丁云喬)                             Time: 14:00~15:00, Jun. 04, 2014

Commentator: Chrong-Reen Wang (王崇任 老師)     Place: Room 601

Abstract:

Rheumatoid arthritis (RA) is a common autoimmune disease in which patient’s joint will not only be eroded but there will also be immune cells infiltration and secretion of inflammatory cytokines resulting in in situ swelling. As a result, the twisted ankle will result in pain and disability. It has been known that T_reg cells play a crucial role in inhibiting the activation of T cells by expressing Foxp3. Recent studies have shown that T_reg cells accumulate in inflammation sites with concurrent unstable Foxp3 expression. By using the artificial collagen induced arthritis mice model (CIA) , the authors in this study determined that FoxP3 expression was repressed in CD25^loFoxp3⁺CD4⁺ T cells resulting in skewing into T_H17 cells (also called exFoxP3 T_H17 cells), which are known to be associated with inflammatory cytokines secretion that plays a key role in inducing arthritis. By examining the T_H17 cell marker and cytokine interleukin (IL)-17 productions, mice containing these transition cells displayed more potent osteoclastic bone erosion than mice with CD25^hiFoxp3⁺CD4⁺ T cells. The synovial fibroblast from CIA mice also released IL-6 which deteriorated the arthritis condition. Moreover the authors observed IL-17⁺Foxp3⁺ T cells in the synovial subset in the secondary immunization with CIA mice, which suggest that plastic Foxp3⁺cells contribute to the pathogenesis of RA. To summarize, the authors discovered that the instability of Foxp3 in T_reg cell will transform these cells into T_H17 cells which contributes to the generation of autoimmune disease.

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