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The histone methyltransferase EZH2 primes the early differentiation of follicular helper T cells during acute viral infection.
Chen, Xiangyu; Cao, Guoshuai; Wu, Jialin; Wang, Xinxin; Pan, Zhiwei; Gao, Jianbao; Tian, Qin; Xu, Lifan; Li, Zhirong; Hao, Yaxing; Huang, Qizhao; Wang, Pengcheng; Xiao, Minglu; Xie, Luoyingzi; Tang, Shupei; Liu, Zhenyu; Hu, Li; Tang, Jianfang; He, Ran; Wang, Li; Zhou, Xinyuan; Wu, Yuzhang; Chen, Mengjie; Sun, Beicheng; Zhu, Bo; Huang, Jun; Ye, Lilin.
Afiliación
  • Chen X; Institute of Immunology, PLA, Third Military Medical University, 400038, Chongqing, China.
  • Cao G; Institute for Molecular Engineering, University of Chicago, Chicago, IL, 60637, USA.
  • Wu J; Institute of Immunology, PLA, Third Military Medical University, 400038, Chongqing, China.
  • Wang X; Institute of Cancer, Xinqiao Hospital, Third Military Medical University, 400038, Chongqing, China.
  • Pan Z; Institute of Immunology, PLA, Third Military Medical University, 400038, Chongqing, China.
  • Gao J; Institute of Cancer, Xinqiao Hospital, Third Military Medical University, 400038, Chongqing, China.
  • Tian Q; Institute of Immunology, PLA, Third Military Medical University, 400038, Chongqing, China.
  • Xu L; Institute of Immunology, PLA, Third Military Medical University, 400038, Chongqing, China.
  • Li Z; Institute of Immunology, PLA, Third Military Medical University, 400038, Chongqing, China.
  • Hao Y; Institute of Immunology, PLA, Third Military Medical University, 400038, Chongqing, China.
  • Huang Q; Cancer Center, The General Hospital of Western Theater Command, Chengdu, China.
  • Wang P; Institute of Immunology, PLA, Third Military Medical University, 400038, Chongqing, China.
  • Xiao M; Institute of Immunology, PLA, Third Military Medical University, 400038, Chongqing, China.
  • Xie L; Institute of Immunology, PLA, Third Military Medical University, 400038, Chongqing, China.
  • Tang S; Institute of Immunology, PLA, Third Military Medical University, 400038, Chongqing, China.
  • Liu Z; Institute of Immunology, PLA, Third Military Medical University, 400038, Chongqing, China.
  • Hu L; Institute of Immunology, PLA, Third Military Medical University, 400038, Chongqing, China.
  • Tang J; Institute of Immunology, PLA, Third Military Medical University, 400038, Chongqing, China.
  • He R; Institute of Immunology, PLA, Third Military Medical University, 400038, Chongqing, China.
  • Wang L; Institute of Immunology, PLA, Third Military Medical University, 400038, Chongqing, China.
  • Zhou X; Institute of Immunology, PLA, Third Military Medical University, 400038, Chongqing, China.
  • Wu Y; Institute of Immunology, PLA, Third Military Medical University, 400038, Chongqing, China.
  • Chen M; Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL, 60637, USA.
  • Sun B; Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210009, Jiangsu, China.
  • Zhu B; Institute of Cancer, Xinqiao Hospital, Third Military Medical University, 400038, Chongqing, China. bo.zhu@tmmu.edu.cn.
  • Huang J; Institute for Molecular Engineering, University of Chicago, Chicago, IL, 60637, USA. huangjun@uchicago.edu.
  • Ye L; Institute of Immunology, PLA, Third Military Medical University, 400038, Chongqing, China. yelilinlcmv@tmmu.edu.cn.
Cell Mol Immunol ; 17(3): 247-260, 2020 03.
Article en En | MEDLINE | ID: mdl-30842630
Epigenetic modifications to histones dictate the differentiation of naïve CD4+ T cells into different subsets of effector T helper (TH) cells. The histone methyltransferase enhancer of zeste homolog 2 (EZH2) has been implicated in the mechanism regulating the differentiation of TH1, TH2 and regulatory T (Treg) cells. However, whether and how EZH2 regulates follicular helper T (TFH) cell differentiation remain unknown. Using a mouse model of acute lymphocytic choriomeningitis virus (LCMV) infection, we observed abundant EZH2 expression and associated H3K27me3 modifications preferentially in the early committed virus-specific TFH cells compared to those in TH1 cells. Ablation of EZH2 in LCMV-specific CD4+ T cells leads to a selective impairment of early TFH cell fate commitment, but not late TFH differentiation or memory TFH maintenance. Mechanistically, EZH2 specifically stabilizes the chromatin accessibility of a cluster of genes that are important for TFH fate commitment, particularly B cell lymphoma 6 (Bcl6), and thus directs TFH cell commitment. Therefore, we identified the chromatin-modifying enzyme EZH2 as a novel regulator of early TFH differentiation during acute viral infection.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diferenciación Celular / Linfocitos T Colaboradores-Inductores / Proteína Potenciadora del Homólogo Zeste 2 / Coriomeningitis Linfocítica / Virus de la Coriomeningitis Linfocítica Límite: Animals Idioma: En Revista: Cell Mol Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: China
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diferenciación Celular / Linfocitos T Colaboradores-Inductores / Proteína Potenciadora del Homólogo Zeste 2 / Coriomeningitis Linfocítica / Virus de la Coriomeningitis Linfocítica Límite: Animals Idioma: En Revista: Cell Mol Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: China