Sumoylation of RORγt regulates T_H17 differentiation and thymocyte development.

ABSTRACT: RORγt controls the differentiation of T_H17 cells, which are mediators of autoimmune conditions such as experimental autoimmune encephalomyelitis (EAE). RORγt also regulates thymocyte development and lymph node genesis. Here we show that the function of RORγt is regulated by its sumoylation. Loss of Sumo3, but not Sumo1, dampens T_H17 differentiation and delays the progression of thymic CD8⁺ immature single-positive cells (ISPs). RORγt is SUMO3-modified by E3 ligase PIAS4 at lysine 31 (K31), and the mutation of K31 to arginine in mice prevents RORγt sumoylation, leading to impaired T_H17 differentiation, resistance to T_H17-mediated EAE, accumulation of thymic ISPs, and a lack of Peyer's patches. Mechanistically, sumoylation of RORγt-K31 r

SUBMITTER: He Z 

PROVIDER: S-EPMC6242824 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature