脱甲基酶
生物
细胞生物学
Notch信号通路
T细胞
细胞
人口
免疫系统
信号转导
免疫学
基因
遗传学
表观遗传学
社会学
人口学
作者
Richard A. Flavell,Chenbo Ding,Zhibin Yu,Hao Xu,Manolis Roulis,Rihao Qu,Jing Zhou,Abigail Jarret,Ruaidhri Jackson,Zheng Wei,Yimeng Gao,Mathias H. Skadow,Esen Sefik,Zhinan Yin,Qiang Zou,Bing Su,Qiang Xia,Huabing Li
标识
DOI:10.21203/rs.3.rs-79739/v1
摘要
Abstract γδ T cells are abundant T cell population at the mucosa and are important in providing immune surveillance as well as maintaining tissue homeostasis. However, despite γδ T cells origin in thymus, detailed mechanisms regulating γδ T cell development remain poorly understood. N 6 -methyladenosine (m 6 A) represents one of the most common post-transcriptional modifications of mRNA in mammalian cells, but whether it plays a role in γδ T cell biology is still unclear. Here we show that depletion of m 6 A demethylase ALKBH5 in lymphocytes specifically induces an expansion of γδ T cells, which confers enhanced protection against gastrointestinal S. typhimurium infection. Mechanistically, loss of ALKBH5 favors the development of γδ T cell precursors by increasing the abundance of m 6 A RNA modification in thymocytes, which further reduces the expression of several target genes including Notch signaling components Jagged1 and Notch2 . As a result, impairment of Jagged1/Notch2 signaling contributes to enhanced proliferation and differentiation of γδ T cell precursors, leading to an expanded mature γδ T cell repertoire. Taken together, our results indicate a checkpoint role of ALKBH5 and m 6 A modification in the regulation of γδ T cell early development.
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