效应器
细胞生物学
细胞毒性T细胞
CD8型
生物
异位表达
细胞分化
免疫系统
免疫学
基因
遗传学
体外
作者
Wenhui Guo,Zhao Wang,Yajiao Zhang,Yashu Li,Qian Du,Tiantian Zhang,Jin Hu,Yingpeng Yao,Jiarui Zhang,Yingdi Xu,Xiao Cui,Zhen Sun,Menghao You,Guotao Yu,Haojian Zhang,Xuguang Du,Jingyu Xu,Shuyang Yu
标识
DOI:10.1016/j.scib.2023.11.029
摘要
Efficient immune responses rely on the proper differentiation of CD8+ T cells into effector and memory cells. Here, we show a critical requirement of N6-Methyladenosine (m6A) methyltransferase Mettl3 during CD8+ T cell responses upon acute viral infection. Conditional deletion of Mettl3 in CD8+ T cells impairs effector expansion and terminal differentiation in an m6A-dependent manner, subsequently affecting memory formation and the secondary response of CD8+ T cells. Our combined RNA-seq and m6A-miCLIP-seq analyses reveal that Mettl3 deficiency broadly impacts the expression of cell cycle and transcriptional regulators. Remarkably, Mettl3 binds to the Tbx21 transcript and stabilizes it, promoting effector differentiation of CD8+ T cells. Moreover, ectopic expression of T-bet partially restores the defects in CD8+ T cell differentiation in the absence of Mettl3. Thus, our study highlights the role of Mettl3 in regulating multiple target genes in an m6A-dependent manner and underscores the importance of m6A modification during CD8+ T cell response.
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