The ubiquitin ligase Peli1 inhibits ICOS and thereby Tfh-mediated immunity.

ABSTRACT: T follicular helper (Tfh) cells are crucial for regulating autoimmune inflammation and protective immunity against viral infection. However, the molecular mechanism controlling Tfh cell differentiation is poorly understood. Here, through two mixed bone marrow chimeric experiments, we identified Peli1, a T cell-enriched E3 ubiquitin ligase, as an intrinsic regulator that inhibits Tfh cell differentiation. Peli1 deficiency significantly promoted c-Rel-mediated inducible T-cell costimulator (ICOS) expression, and PELI1 mRNA expression was negatively associated with ICOS expression on human CD4⁺ T cells. Mechanistically, increased ICOS expression on Peli1-KO CD4⁺ T cells enhanced the activation of PI3K-AKT signaling and thus suppressed the expression of Klf2, a transcript

SUBMITTER: Huang X 

PROVIDER: S-EPMC8115645 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature