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.