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

Th17 cells are potent mediators in autoimmune diseases, and RORgt is required for their development. Recent studies have shown that ROR gamma t(+) Treg cells in the gut regulate intestinal inflammation by inhibiting effector T cell function. In the current study, we report that ROR gamma t(+) Treg cells were also found in lymph nodes following immunization. Not only distinct from intestinal ROR gamma t(+) Treg cells in their transcriptomes, peripheral ROR gamma t(+) Treg cells were derived from Foxp3(+) thymic Treg cells in an antigen-specific manner. Development of these ROR gamma t(+) 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.