The nuclear receptor REV-ERB? modulates Th17 cell-mediated autoimmune disease.

ABSTRACT: T helper 17 (Th17) cells produce interleukin-17 (IL-17) cytokines and drive inflammatory responses in autoimmune diseases such as multiple sclerosis. The differentiation of Th17 cells is dependent on the retinoic acid receptor-related orphan nuclear receptor ROR?t. Here, we identify REV-ERB? (encoded by Nr1d1), a member of the nuclear hormone receptor family, as a transcriptional repressor that antagonizes ROR?t function in Th17 cells. REV-ERB? binds to ROR response elements (RORE) in Th17 cells and inhibits the expression of ROR?t-dependent genes including Il17a and Il17f Furthermore, elevated REV-ERB? expression or treatment with a synthetic REV-ERB agonist significantly delays the onset and impedes the progression of experimental autoimmune encephalomyelitis (EAE). These results suggest that modulating REV-ERB? activity may be used to manipulate Th17 cells in autoimmune diseases.

SUBMITTER: Chang C 

PROVIDER: S-EPMC6744854 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature