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...
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Frontiers Media S.A.
2022-08-01
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Series: | Frontiers in Immunology |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.942465/full |
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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.
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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 |
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