FTO controls CD8⁺ T cell survival and effector response by modulating m⁶A methylation of Fas.

ABSTRACT: Functional CD8⁺ T cell immunity is essential for immune surveillance and host defense against infection and tumors. Epigenetic mechanisms, particularly RNA modification, in controlling CD8⁺ T cell immune response is not fully elucidated. Here, by T cell-specific deletion of fat mass and obesity-associated protein (FTO), a critical N6-methyladenosine (m⁶A) demethylase, we revealed that FTO was indispensable for adequate CD8⁺ T cell immune response and protective function. FTO ablation led to considerable cell death in activated CD8⁺ T cells, which was attributed to cell apoptosis. MeRIP-seq analysis revealed an increase in m⁶A methylation on Fas mRNA in FTO-deficient CD8⁺ T cells. The loss of FTO promoted Fas expre

SUBMITTER: Sun L 

PROVIDER: S-EPMC12000336 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature