Mettl3-dependent m6A modification is essential for effector differentiation and memory formation of CD8+ T cells [SLIM-seq]

The goal of this study is to determine the critical requirement of N6-Methyladenosine (m6A) methyltransferase Mettl3 during CD8+ T cell responses upon acute viral infection. We demonstrate that conditional ablation of Mettl3 in CD8+ T cells impairs effector expansion and terminal differentiation in an m6A-dependent manner, which in turn affects memory formation and secondary response. Mechanism analysis indicates that Mettl3 deficiency broadly affects expression of cell cycle and transcriptional regulators. Based on these findings, our study reveals the important role of m6A modification in CD8+ T cell responses. Overall design: Wild-type naïve (CD44-CD62L+) CD8+ T cells (3 samples per group), effector (CD44+CD62L-) CD8+ T cells (3 samples per group) and memory (CD44+CD62L+) CD8+ T cells (3 samples per group) were sorted

本研究旨在明确N6-甲基腺苷（N6-Methyladenosine, m6A）甲基转移酶Mettl3在急性病毒感染诱导的CD8+ T细胞应答中的关键功能需求。研究证实，CD8+ T细胞中Mettl3的条件性敲除会以m6A依赖的方式损害效应细胞扩增与终末分化，进而影响记忆细胞形成及继发应答。机制分析表明，Mettl3缺失会广泛影响细胞周期与转录调控因子的表达。基于上述发现，本研究揭示了m6A修饰在CD8+ T细胞应答中的重要作用。实验整体设计：分选获取野生型初始（CD44-CD62L+）CD8+ T细胞（每组3份样本）、效应性（CD44+CD62L-）CD8+ T细胞（每组3份样本）及记忆性（CD44+CD62L+）CD8+ T细胞（每组3份样本）。