核糖核酸
生物
免疫系统
病毒
病毒学
癌症研究
先天免疫系统
溶瘤病毒
干扰素
病毒复制
免疫监视
作者
Shoubao Ma,Jiazhuo Yan,Tasha Barr,Jianying Zhang,Zhenhua Chen,Li-Shu Wang,Joseph C. Sun,Jianjun Chen,Michael A. Caligiuri,Jianhua Yu
标识
DOI:10.1101/2021.04.26.441557
摘要
Abstract N6-methyladenosine (m6A) is the most prevalent post-transcriptional modification on RNA. NK cells are the predominant innate lymphoid cells that mediate anti-viral and anti-tumor immunity. However, whether and how m6A modifications affect NK cell immunity remains unknown. Here, we discover that YTHDF2, a well-known m6A reader, is upregulated in NK cells upon activation by cytokines, tumors, and cytomegalovirus infection. Ythdf2 deficiency in NK cells impairs NK cell anti-tumor and anti-viral activity in vivo. YTHDF2 maintains NK cell homeostasis and terminal maturation, correlating with modulating NK cell trafficking and regulating Eomes, respectively. YTHDF2 promotes NK cell effector function and is required for IL-15-mediated NK cell survival and proliferation by forming a STAT5-YTHDF2 positive feedback loop. Transcriptome-wide screening identifies Tardbp to be involved in cell proliferation or survival as a YTHDF2-binding target in NK cells. Collectively, we elucidate the biological roles of m6A modifications in NK cells and highlight a new direction to harness NK cell anti-tumor immunity.
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