The Epigenetic Regulator EZH2 Instructs CD4 T Cell Response to Acute Viral Infection via Coupling of Cell Expansion and Metabolic Fitness

文献类型： 外文期刊

第一作者： Li, Ren

作者： Li, Ren;Shan, Lingling;Liu, Pinghuang;Li, Ren;Wei, Ping;Pan, Zhiwei;Yue, Shuai;Lin, Yao;Yang, Yang;Li, Zhirong;Hu, Li;Tang, Jianfang;Tian, Qin;Ye, Lilin;Chen, Xiangyu;Wu, Jialin;Jiang, Peng;Chen, Xiangyu;Liu, Pinghuang

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关键词： acute viral infection; EZH2; CD4 T cell expansion; mTOR; metabolism

期刊名称：JOURNAL OF VIROLOGY （ 影响因子：5.103； 五年影响因子：5.078 ）

ISSN： 0022-538X

年卷期： 2020 年 94 卷 24 期

页码：

收录情况： SCI

摘要： The protection of a majority of viral vaccines is mediated by CD4 T cell dependent humoral immunity. The methyltransferase enhancer of zeste homolog 2 (EZH2) dictates the differentiation of naive CD4 T cells into distinct effector T helper subsets at the onset of acute viral infection. However, whether and how EZH2 manipulates differentiated virus-specific CD4 T cell expansion remain to be elucidated. Here, we found that EZH2 is integral for virus-specific CD4 T cell expansion in a mouse model of acute viral infection. By a mechanism that involves fine-tuning the mechanistic target of rapamycin (mTOR) signaling, EZH2 participates in integrating metabolic pathways to support cell expansion. The genetic ablation of EZH2 leads to impaired cellular metabolism and, consequently, poor CD4 T cell response to acute viral infection. Thus, we identified EZH2 as a novel regulator in virus-specific CD4 T cell expansion during acute viral infection. IMPORTANCE The CD4 T cell response is critical in curtailing viral infection or eliciting efficacious viral vaccination. Highly efficient expansion of virus-specific CD4 T cells culminates in a qualified CD4 T cell response. Here, we found that the epigenetic regulator EZH2 is a prerequisite for the virus-specific CD4 T cell response, with a mechanism coupling cell expansion and metabolism. Thus, our study provides valuable insights for strategies targeting EZH2 to improve the efficacy of CD4 T cell based viral vaccines and to help treat diseases associated with aberrant CD4 T cell responses.

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