Citation

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Generation of RORt(+) Antigen-Specific T Regulatory 17 Cells from Foxp3(+) Precursors in Autoimmunity.

Kim, BS;Lu, H;Ichiyama, K;Chen, X;Zhang, YB;Mistry, NA;Tanaka, K;Lee, YH;Nurieva, R;Zhang, L;Yang, X;Chung, Y;Jin, W;Chang, SH;Dong, C;

Th17 cells are potent mediators in autoimmune diseases, and RORt is required for their development. Recent studies have shown that RORt(+) Treg cells in the gut regulate intestinal inflammation by inhibiting effector T cell function. In the current study, we report that RORt(+) Treg cells were also found in lymph nodes following immunization. Not only distinct from intestinal RORt(+) Treg cells in their transcriptomes, peripheral RORt(+) Treg cells were derived from Foxp3(+) thymic Treg cells in an antigen-specific manner. Development of these RORt(+) Treg cells, coined T regulatory 17 (Tr17) cells, depended on IL-6/Stat3 signaling. Tr17 cells showed suppressive activity against antigen-specific effector T cells in vitro. In addition, Tr17 cells efficiently inhibited myelin-specific Th17-cell-mediated CNS auto-inflammation in a passive EAE model. Collectively, our study demonstrates that Tr17 cells are effector Treg cells that potentially restrict autoimmunity.