Decoupling the role of RORγt in the differentiation and effector function of T_H17 cells.

ABSTRACT: RORγt is known to instruct the differentiation of T helper 17 (T_H17) cells that mediate the pathogenesis of autoimmune diseases. However, it remains unknown whether RORγt plays a distinct role in the differentiation and effector function of T_H17 cells. Here, we show that mutation of RORγt lysine-256, a ubiquitination site, to arginine (K256R) separates the RORγt role in these two functions. Preventing ubiquitination at K256 via arginine substitution does not affect RORγt-dependent thymocyte development, and T_H17 differentiation in vitro and in vivo, however, greatly impaired the pathogenesis of T_H17 cell-mediated experimental autoimmune encephalomyelitis (EAE). Mechanistically, K256R mutation impairs RORγt to bind to and activate Runx1 exp

SUBMITTER: Zhong X 

PROVIDER: S-EPMC9586477 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature