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

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外文摘要：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 dur-ing 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 tran-scriptional regulators.Remarkably,Mettl3 binds to the Tbx21 transcript and stabilizes it,promoting effec-tor 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 reg-ulating multiple target genes in an m6A-dependent manner and underscores the importance of m6A mod-ification during CD8+T cell response.

外文关键词：

CD8+T cellT cell responseMettl3m6AEffectorMemory

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

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作者单位：

State Key Laboratory of Animal Biotech Breeding,College of Biological Sciences,China Agricultural University,Beijing 100193,China

Frontier Science Center for Immunology and Metabolism,Medical Research Institute,School of Medicine,Wuhan University,Wuhan 430071,China

The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi Medical University,Zunyi 563000,China

基金：

National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Key Research and Development Program of ChinaPinduoduo-China Agricultural University Research FundFrontiers Science Center for Molecular Design Breeding(MOE)Chinese Universities Scientific FundChinese Universities Scientific FundProject for Extramural Scientists of State Key Laboratory of Agrobiotechnology from China Agricultural UniversityProject for Extramural Scientists of State Key Laboratory of Agrobiotechnology from China Agricultural UniversityCollaborative Innovation Center of Chinese Ministry of Education

项目编号：

32130039319708318197054131960151316300382017YFA0104401PC2023B010112022TC0302021TC0872021SKLAB6-32021SKLAB6-42020-39

出版年：

2024

DOI：

10.1016/j.scib.2023.11.029

科学通报(英文版)

中国科学院

科学通报(英文版)

CSTPCD

ISSN：1001-6538

年,卷(期)：2024.69(1)

参考文献量62