EZH2 restricts Tcf7 DNA methylation and promotes TFH differentiation during acute viral infection

Follicular helper T (TFH) cells provide specialized help for B cells to ensure optimal humoral immunity. The histone methyltransferase EZH2, as a chromatin repressor, secures the TFH differentiation by promoting TFH lineage associated gene expression during acute viral infection, including Tcf7 and...

Full description

Bibliographic Details
Main Authors: Yuan Luo, Dan Li, Luoyingzi Xie, Shun Lei, Xiangyu Chen, Cong Wang, Dong Yao, Lin Li, Jingyi Fang, Cheng Chen, Shijie Yuan, Fei Li, Xiaorong Xie, Yan Zhang, Zhirong Li, Li Hu, Jianfang Tang, Lilin Ye, Zhengping Wei, Ran He
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-08-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2022.942465/full
_version_ 1811320878233812992
author Yuan Luo
Yuan Luo
Dan Li
Luoyingzi Xie
Shun Lei
Xiangyu Chen
Cong Wang
Dong Yao
Lin Li
Jingyi Fang
Cheng Chen
Shijie Yuan
Fei Li
Xiaorong Xie
Yan Zhang
Zhirong Li
Li Hu
Jianfang Tang
Lilin Ye
Zhengping Wei
Zhengping Wei
Ran He
author_facet Yuan Luo
Yuan Luo
Dan Li
Luoyingzi Xie
Shun Lei
Xiangyu Chen
Cong Wang
Dong Yao
Lin Li
Jingyi Fang
Cheng Chen
Shijie Yuan
Fei Li
Xiaorong Xie
Yan Zhang
Zhirong Li
Li Hu
Jianfang Tang
Lilin Ye
Zhengping Wei
Zhengping Wei
Ran He
author_sort Yuan Luo
collection DOAJ
description Follicular helper T (TFH) cells provide specialized help for B cells to ensure optimal humoral immunity. The histone methyltransferase EZH2, as a chromatin repressor, secures the TFH differentiation by promoting TFH lineage associated gene expression during acute viral infection, including Tcf7 and Bcl6. By using conditional deletion murine system, we observed that EZH2 ablation in CD4+ T cells was accompanied by aberrant accumulation of DNA methyltransferases (DNMTs) DNMT1 and DNMT3B in TFH cells. And the loss of EZH2 promoted aggravation of DNA methylation status at Tcf7 locus. Therefore, our findings suggested that EZH2 plays an important role in maintenance of hypomethylation at Tcf7 locus thus affecting TFH differentiation during acute viral infection.
first_indexed 2024-04-13T13:08:17Z
format Article
id doaj.art-5a4f485248a44085a905a29847f0471e
institution Directory Open Access Journal
issn 1664-3224
language English
last_indexed 2024-04-13T13:08:17Z
publishDate 2022-08-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Immunology
spelling doaj.art-5a4f485248a44085a905a29847f0471e2022-12-22T02:45:42ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-08-011310.3389/fimmu.2022.942465942465EZH2 restricts Tcf7 DNA methylation and promotes TFH differentiation during acute viral infectionYuan Luo0Yuan Luo1Dan Li2Luoyingzi Xie3Shun Lei4Xiangyu Chen5Cong Wang6Dong Yao7Lin Li8Jingyi Fang9Cheng Chen10Shijie Yuan11Fei Li12Xiaorong Xie13Yan Zhang14Zhirong Li15Li Hu16Jianfang Tang17Lilin Ye18Zhengping Wei19Zhengping Wei20Ran He21Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Immunology, Third Military Medical University, Chongqing, ChinaDepartment of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Immunology, Third Military Medical University, Chongqing, ChinaInstitute of Immunology, Third Military Medical University, Chongqing, ChinaInstitute of Immunology, Third Military Medical University, Chongqing, ChinaChongqing General Hospital, University of Chinese Academy of Sciences, Chongqing, ChinaDepartment of Anesthesiology, Chongqing Public Health Medical Center, Chongqing, ChinaDepartment of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Immunology, Third Military Medical University, Chongqing, ChinaInstitute of Immunology, Third Military Medical University, Chongqing, ChinaDepartment of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Immunology, Third Military Medical University, Chongqing, ChinaInstitute of Immunology, Third Military Medical University, Chongqing, ChinaInstitute of Immunology, Third Military Medical University, Chongqing, ChinaInstitute of Immunology, Third Military Medical University, Chongqing, ChinaInstitute of Immunology, Third Military Medical University, Chongqing, ChinaInstitute of Immunology, Third Military Medical University, Chongqing, ChinaDermatology Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaFollicular helper T (TFH) cells provide specialized help for B cells to ensure optimal humoral immunity. The histone methyltransferase EZH2, as a chromatin repressor, secures the TFH differentiation by promoting TFH lineage associated gene expression during acute viral infection, including Tcf7 and Bcl6. By using conditional deletion murine system, we observed that EZH2 ablation in CD4+ T cells was accompanied by aberrant accumulation of DNA methyltransferases (DNMTs) DNMT1 and DNMT3B in TFH cells. And the loss of EZH2 promoted aggravation of DNA methylation status at Tcf7 locus. Therefore, our findings suggested that EZH2 plays an important role in maintenance of hypomethylation at Tcf7 locus thus affecting TFH differentiation during acute viral infection. https://www.frontiersin.org/articles/10.3389/fimmu.2022.942465/fullLCMVTFH cellsEZH2DNA methylationTcf7
spellingShingle Yuan Luo
Yuan Luo
Dan Li
Luoyingzi Xie
Shun Lei
Xiangyu Chen
Cong Wang
Dong Yao
Lin Li
Jingyi Fang
Cheng Chen
Shijie Yuan
Fei Li
Xiaorong Xie
Yan Zhang
Zhirong Li
Li Hu
Jianfang Tang
Lilin Ye
Zhengping Wei
Zhengping Wei
Ran He
EZH2 restricts Tcf7 DNA methylation and promotes TFH differentiation during acute viral infection
Frontiers in Immunology
LCMV
TFH cells
EZH2
DNA methylation
Tcf7
title EZH2 restricts Tcf7 DNA methylation and promotes TFH differentiation during acute viral infection
title_full EZH2 restricts Tcf7 DNA methylation and promotes TFH differentiation during acute viral infection
title_fullStr EZH2 restricts Tcf7 DNA methylation and promotes TFH differentiation during acute viral infection
title_full_unstemmed EZH2 restricts Tcf7 DNA methylation and promotes TFH differentiation during acute viral infection
title_short EZH2 restricts Tcf7 DNA methylation and promotes TFH differentiation during acute viral infection
title_sort ezh2 restricts tcf7 dna methylation and promotes tfh differentiation during acute viral infection
topic LCMV
TFH cells
EZH2
DNA methylation
Tcf7
url https://www.frontiersin.org/articles/10.3389/fimmu.2022.942465/full
work_keys_str_mv AT yuanluo ezh2restrictstcf7dnamethylationandpromotestfhdifferentiationduringacuteviralinfection
AT yuanluo ezh2restrictstcf7dnamethylationandpromotestfhdifferentiationduringacuteviralinfection
AT danli ezh2restrictstcf7dnamethylationandpromotestfhdifferentiationduringacuteviralinfection
AT luoyingzixie ezh2restrictstcf7dnamethylationandpromotestfhdifferentiationduringacuteviralinfection
AT shunlei ezh2restrictstcf7dnamethylationandpromotestfhdifferentiationduringacuteviralinfection
AT xiangyuchen ezh2restrictstcf7dnamethylationandpromotestfhdifferentiationduringacuteviralinfection
AT congwang ezh2restrictstcf7dnamethylationandpromotestfhdifferentiationduringacuteviralinfection
AT dongyao ezh2restrictstcf7dnamethylationandpromotestfhdifferentiationduringacuteviralinfection
AT linli ezh2restrictstcf7dnamethylationandpromotestfhdifferentiationduringacuteviralinfection
AT jingyifang ezh2restrictstcf7dnamethylationandpromotestfhdifferentiationduringacuteviralinfection
AT chengchen ezh2restrictstcf7dnamethylationandpromotestfhdifferentiationduringacuteviralinfection
AT shijieyuan ezh2restrictstcf7dnamethylationandpromotestfhdifferentiationduringacuteviralinfection
AT feili ezh2restrictstcf7dnamethylationandpromotestfhdifferentiationduringacuteviralinfection
AT xiaorongxie ezh2restrictstcf7dnamethylationandpromotestfhdifferentiationduringacuteviralinfection
AT yanzhang ezh2restrictstcf7dnamethylationandpromotestfhdifferentiationduringacuteviralinfection
AT zhirongli ezh2restrictstcf7dnamethylationandpromotestfhdifferentiationduringacuteviralinfection
AT lihu ezh2restrictstcf7dnamethylationandpromotestfhdifferentiationduringacuteviralinfection
AT jianfangtang ezh2restrictstcf7dnamethylationandpromotestfhdifferentiationduringacuteviralinfection
AT lilinye ezh2restrictstcf7dnamethylationandpromotestfhdifferentiationduringacuteviralinfection
AT zhengpingwei ezh2restrictstcf7dnamethylationandpromotestfhdifferentiationduringacuteviralinfection
AT zhengpingwei ezh2restrictstcf7dnamethylationandpromotestfhdifferentiationduringacuteviralinfection
AT ranhe ezh2restrictstcf7dnamethylationandpromotestfhdifferentiationduringacuteviralinfection