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 the world. Within the disease, patient’s joint not only eroded by the cells but also see the immune cells infiltration and secrete inflammatory cytokines to cause in situ swelling. The twisting ankle will result in pain and disable. As we already knows that, T_reg cell is the crucial role inhibit the activation of T cells like the breaking system by the expressing Foxp3. In recent studies shows that it accumulate in the inflammation sites with the unstable Foxp3 expression. By using the artificial collagen induced arthritis mice (CIA) , the author find that CD25^loFoxp3⁺CD4⁺ T cells will lost the Foxp3 (called exFoxp3) then skew into T_H17 cells, which also 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 producing, this transition cells show more potent in osteoclastic bone erosion than CD25^hiFoxp3⁺CD4⁺ T cells, which still have the inhibition ability. Besides, the synovial fibroblast also release the IL-6 to deteriorate the arthritis condition. Moreover they observe the IL-17⁺Foxp3⁺ T cells in the synovial subset in the secondary immunization with collagen mice, which suggest that plastic Foxp3⁺ cells contribute to the pathogenesis of RA. To sum up, they find the instability of Foxp3 in T_reg cell will transform into T_H17 cells in the generation of autoimmune disease.

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