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

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 15, 2025

Abstract Functional CD8 + T cell immunity is essential for immune surveillance and host defense against infection tumors. Epigenetic mechanisms, particularly RNA modification, in controlling response not fully elucidated. Here, by cell-specific deletion of fat mass obesity-associated protein (FTO), a critical N6-methyladenosine (m 6 A) demethylase, we revealed that FTO was indispensable adequate protective function. ablation led to considerable death activated cells, which attributed apoptosis. MeRIP-seq analysis an increase m A methylation on Fas mRNA FTO-deficient cells. The loss promoted expression via enhancing the stability, depended reader insulin-like growth factor-2 mRNA-biding proteins 3 (IGF2BP3). Mutation sites or knockdown IGF2BP3 could normalize upregulated apoptosis levels caused Our findings delineate novel epigenetic regulatory mechanism FTO-mediated modification supporting survival effector responses, providing new insights into understanding post-transcriptional regulation immunological functions potential therapeutic intervention.

Language: Английский

The m6A demethylase FTO controls Th1 differentiation and immunity against infections

Molecular Immunology, Journal Year: 2025, Volume and Issue: 183, P. 172 - 181

Published: May 15, 2025

Language: Английский