The E3 ligase VHL promotes follicular helper T cell differentiation via glycolytic-epigenetic control.

ABSTRACT: Follicular helper T (Tfh) cells are essential for germinal center formation and effective humoral immunity, which undergo different stages of development to become fully polarized. However, the detailed mechanisms of their regulation remain unsolved. Here we found that the E3 ubiquitin ligase VHL was required for Tfh cell development and function upon acute virus infection or antigen immunization. VHL acted through the hypoxia-inducible factor 1α (HIF-1α)-dependent glycolysis pathway to positively regulate early Tfh cell initiation. The enhanced glycolytic activity due to VHL deficiency was involved in the epigenetic regulation of ICOS expression, a critical molecule for Tfh development. By using an RNA interference screen, we identified the glycolytic enzyme GAPDH as the key target for th

SUBMITTER: Zhu Y 

PROVIDER: S-EPMC6605754 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature