REV-ERBα Regulates T_H17 Cell Development and Autoimmunity.

ABSTRACT: RORγt is well recognized as the lineage-defining transcription factor for T helper 17 (T_H17) cell development. However, the cell-intrinsic mechanisms that negatively regulate T_H17 cell development and autoimmunity remain poorly understood. Here, we demonstrate that the transcriptional repressor REV-ERBα is exclusively expressed in T_H17 cells, competes with RORγt for their shared DNA consensus sequence, and negatively regulates T_H17 cell development via repression of genes traditionally characterized as RORγt dependent, including Il17a. Deletion of REV-ERBα enhanced T_H17-mediated pro-inflammatory cytokine expression, exacerbating experimental autoimmune encephalomyelitis (EAE) and colitis. Treatment with REV-ERB-specific synthetic ligan

SUBMITTER: Amir M 

PROVIDER: S-EPMC6400287 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature