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.