Generation of RORγt+ Antigen-Specific T Regulatory 17 Cells from Foxp3+ Precursors in Autoimmunity

Publication date: 3 October 2017
Source:Cell Reports, Volume 21, Issue 1
Author(s): Byung-Seok Kim, Huiping Lu, Kenji Ichiyama, Xiang Chen, Yi-Bing Zhang, Nipun A. Mistry, Kentaro Tanaka, Young-hee Lee, Roza Nurieva, Li Zhang, Xuexian Yang, Yeonseok Chung, Wei Jin, Seon Hee Chang, Chen Dong
Th17 cells are potent mediators in autoimmune diseases, and RORγt is required for their development. Recent studies have shown that RORγt⁺ Treg cells in the gut regulate intestinal inflammation by inhibiting effector T cell function. In the current study, we report that RORγt⁺ Treg cells were also found in lymph nodes following immunization. Not only distinct from intestinal RORγt⁺ Treg cells in their transcriptomes, peripheral RORγt⁺ Treg cells were derived from Foxp3⁺ thymic Treg cells in an antigen-specific manner. Development of these RORγt⁺ 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.

Graphical abstract

Teaser

Kim et al. find that RORγt⁺Foxp3⁺ T regulatory 17 (Tr17) cells are induced in lymph nodes after immunization. Tr17 cells are generated from thymic Treg cells in an antigen-specific manner through Stat3 signaling. Their data suggest that Tr17 cells represent antigen-specific effector Treg cells that can regulate Th17-cell-dependent autoimmunity.


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