The histone methyltransferase EZH2 primes the early differentiation of follicular helper T cells during acute viral infection

Epigenetic modifications to histones dictate the differentiation of naïve CD4(+) T cells into different subsets of effector T helper (T(H)) cells. The histone methyltransferase enhancer of zeste homolog 2 (EZH2) has been implicated in the mechanism regulating the differentiation of T(H)1, T(H)2 and...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052164/
https://www.ncbi.nlm.nih.gov/pubmed/30842630
http://dx.doi.org/10.1038/s41423-019-0219-z
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author 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
author_facet 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
author_sort Chen, Xiangyu
collection PubMed
description Epigenetic modifications to histones dictate the differentiation of naïve CD4(+) T cells into different subsets of effector T helper (T(H)) cells. The histone methyltransferase enhancer of zeste homolog 2 (EZH2) has been implicated in the mechanism regulating the differentiation of T(H)1, T(H)2 and regulatory T (T(reg)) cells. However, whether and how EZH2 regulates follicular helper T (T(FH)) 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 T(FH) cells compared to those in T(H)1 cells. Ablation of EZH2 in LCMV-specific CD4(+) T cells leads to a selective impairment of early T(FH) cell fate commitment, but not late T(FH) differentiation or memory T(FH) maintenance. Mechanistically, EZH2 specifically stabilizes the chromatin accessibility of a cluster of genes that are important for T(FH) fate commitment, particularly B cell lymphoma 6 (Bcl6), and thus directs T(FH) cell commitment. Therefore, we identified the chromatin-modifying enzyme EZH2 as a novel regulator of early T(FH) differentiation during acute viral infection.
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spelling pubmed-70521642020-03-05 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 Cell Mol Immunol Article Epigenetic modifications to histones dictate the differentiation of naïve CD4(+) T cells into different subsets of effector T helper (T(H)) cells. The histone methyltransferase enhancer of zeste homolog 2 (EZH2) has been implicated in the mechanism regulating the differentiation of T(H)1, T(H)2 and regulatory T (T(reg)) cells. However, whether and how EZH2 regulates follicular helper T (T(FH)) 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 T(FH) cells compared to those in T(H)1 cells. Ablation of EZH2 in LCMV-specific CD4(+) T cells leads to a selective impairment of early T(FH) cell fate commitment, but not late T(FH) differentiation or memory T(FH) maintenance. Mechanistically, EZH2 specifically stabilizes the chromatin accessibility of a cluster of genes that are important for T(FH) fate commitment, particularly B cell lymphoma 6 (Bcl6), and thus directs T(FH) cell commitment. Therefore, we identified the chromatin-modifying enzyme EZH2 as a novel regulator of early T(FH) differentiation during acute viral infection. Nature Publishing Group UK 2019-03-06 2020-03 /pmc/articles/PMC7052164/ /pubmed/30842630 http://dx.doi.org/10.1038/s41423-019-0219-z Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
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
The histone methyltransferase EZH2 primes the early differentiation of follicular helper T cells during acute viral infection
title The histone methyltransferase EZH2 primes the early differentiation of follicular helper T cells during acute viral infection
title_full The histone methyltransferase EZH2 primes the early differentiation of follicular helper T cells during acute viral infection
title_fullStr The histone methyltransferase EZH2 primes the early differentiation of follicular helper T cells during acute viral infection
title_full_unstemmed The histone methyltransferase EZH2 primes the early differentiation of follicular helper T cells during acute viral infection
title_short The histone methyltransferase EZH2 primes the early differentiation of follicular helper T cells during acute viral infection
title_sort histone methyltransferase ezh2 primes the early differentiation of follicular helper t cells during acute viral infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052164/
https://www.ncbi.nlm.nih.gov/pubmed/30842630
http://dx.doi.org/10.1038/s41423-019-0219-z
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