Generation of RORγt+ antigen-specific T regulatory 17 (Tr17) 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 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 as 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 Tr17 cells as effector Treg cells that potentially restrict autoimmunity. Examination of mRNA profiles of RORγt+ Tr17 cells in draining lymph nodes of immunized mice by deep sequencing, using SOLiD v4