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Generation of ROR?t+ Antigen-Specific T Regulatory 17 Cells from Foxp3+ Precursors in Autoimmunity.


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

SUBMITTER: Kim BS 

PROVIDER: S-EPMC5716359 | BioStudies | 2017-01-01

REPOSITORIES: biostudies

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