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

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. [Display omitted] •RORγt+Foxp3+CD4+ Tr17 cells are found in lymph nodes after immunization•Tr17 cells upregulate Treg cell-associated effector molecules and CCR6•Tr17 cells originate from resting Treg cells via Stat3 signaling•Tr17 cells potentially modulate Th17-cell-driven CNS autoimmunity 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.