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 r...
Gespeichert in:
| Veröffentlicht in: | Cellular & molecular immunology 2020-03, Vol.17 (3), p.247-260 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 260 |
|---|---|
| container_issue | 3 |
| container_start_page | 247 |
| container_title | Cellular & molecular immunology |
| container_volume | 17 |
| creator | 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 |
| 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. |
| doi_str_mv | 10.1038/s41423-019-0219-z |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7052164</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2369855583</sourcerecordid><originalsourceid>FETCH-LOGICAL-c470t-9c476c12ac090a1b887b8a31777b49095009ba09629720cf97e91efeb98006f3</originalsourceid><addsrcrecordid>eNp1kU1r3DAQhkVpaTZpf0AvRdBLL25Hsq2PS6GEtCkEetlTL0LWjrIKWmsr2YEN5L9XZpP0A3qREPPMO_PqJeQNgw8MWvWxdKzjbQNMN8DrcfeMrDh0vL64eE5WTEjeSKHYCTkt5QagV53sXpKTFlTHRQsrcr_eIt2GMqUR6Q6n7SFO2Y7FY7YF6cWPS073Oeyw0KmSaHM80E3wtY7jFOwU0kiTpz7FGNwcbaZbjHvMdE0dxljoZs5hvKbWzRPS25BtpGH06JbOV-SFt7Hg64f7jKy_XKzPL5ur71-_nX--alwnYWp0vYRj3DrQYNmglByUbZmUcug06B5ADxa04FpycF5L1Aw9DloBCN-ekU9H2f087HDj6uZ1DbP4svlgkg3m78oYtuY63RoJPWeiqwLvHwRy-jljmcwulMWeHTHNxXCmVJ2ltKjou3_QmzTnsbozvBVa9X2v2kqxI-VyKiWjf1qGgVmyNcdsTc3WLNmau9rz9k8XTx2PYVaAH4GyX74c8-_R_1f9BfGjscs</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2369855583</pqid></control><display><type>article</type><title>The histone methyltransferase EZH2 primes the early differentiation of follicular helper T cells during acute viral infection</title><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>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</creator><creatorcontrib>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</creatorcontrib><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.</description><identifier>ISSN: 1672-7681</identifier><identifier>EISSN: 2042-0226</identifier><identifier>DOI: 10.1038/s41423-019-0219-z</identifier><identifier>PMID: 30842630</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/250/2152/1566/2493 ; 631/250/2499 ; 631/250/254 ; Antibodies ; Bcl-6 protein ; Biomedical and Life Sciences ; Biomedicine ; CD4 antigen ; Cell differentiation ; Cell fate ; Chromatin ; Effector cells ; Histone methyltransferase ; Histones ; Immunology ; Infections ; Lymphocytes ; Lymphocytes T ; Medical Microbiology ; Microbiology ; Vaccine ; Viral infections</subject><ispartof>Cellular & molecular immunology, 2020-03, Vol.17 (3), p.247-260</ispartof><rights>The Author(s) 2019</rights><rights>This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c470t-9c476c12ac090a1b887b8a31777b49095009ba09629720cf97e91efeb98006f3</citedby><cites>FETCH-LOGICAL-c470t-9c476c12ac090a1b887b8a31777b49095009ba09629720cf97e91efeb98006f3</cites><orcidid>0000-0003-0778-3311</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052164/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052164/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,725,778,782,883,27907,27908,53774,53776</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30842630$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Xiangyu</creatorcontrib><creatorcontrib>Cao, Guoshuai</creatorcontrib><creatorcontrib>Wu, Jialin</creatorcontrib><creatorcontrib>Wang, Xinxin</creatorcontrib><creatorcontrib>Pan, Zhiwei</creatorcontrib><creatorcontrib>Gao, Jianbao</creatorcontrib><creatorcontrib>Tian, Qin</creatorcontrib><creatorcontrib>Xu, Lifan</creatorcontrib><creatorcontrib>Li, Zhirong</creatorcontrib><creatorcontrib>Hao, Yaxing</creatorcontrib><creatorcontrib>Huang, Qizhao</creatorcontrib><creatorcontrib>Wang, Pengcheng</creatorcontrib><creatorcontrib>Xiao, Minglu</creatorcontrib><creatorcontrib>Xie, Luoyingzi</creatorcontrib><creatorcontrib>Tang, Shupei</creatorcontrib><creatorcontrib>Liu, Zhenyu</creatorcontrib><creatorcontrib>Hu, Li</creatorcontrib><creatorcontrib>Tang, Jianfang</creatorcontrib><creatorcontrib>He, Ran</creatorcontrib><creatorcontrib>Wang, Li</creatorcontrib><creatorcontrib>Zhou, Xinyuan</creatorcontrib><creatorcontrib>Wu, Yuzhang</creatorcontrib><creatorcontrib>Chen, Mengjie</creatorcontrib><creatorcontrib>Sun, Beicheng</creatorcontrib><creatorcontrib>Zhu, Bo</creatorcontrib><creatorcontrib>Huang, Jun</creatorcontrib><creatorcontrib>Ye, Lilin</creatorcontrib><title>The histone methyltransferase EZH2 primes the early differentiation of follicular helper T cells during acute viral infection</title><title>Cellular & molecular immunology</title><addtitle>Cell Mol Immunol</addtitle><addtitle>Cell Mol Immunol</addtitle><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.</description><subject>631/250/2152/1566/2493</subject><subject>631/250/2499</subject><subject>631/250/254</subject><subject>Antibodies</subject><subject>Bcl-6 protein</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>CD4 antigen</subject><subject>Cell differentiation</subject><subject>Cell fate</subject><subject>Chromatin</subject><subject>Effector cells</subject><subject>Histone methyltransferase</subject><subject>Histones</subject><subject>Immunology</subject><subject>Infections</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Medical Microbiology</subject><subject>Microbiology</subject><subject>Vaccine</subject><subject>Viral infections</subject><issn>1672-7681</issn><issn>2042-0226</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kU1r3DAQhkVpaTZpf0AvRdBLL25Hsq2PS6GEtCkEetlTL0LWjrIKWmsr2YEN5L9XZpP0A3qREPPMO_PqJeQNgw8MWvWxdKzjbQNMN8DrcfeMrDh0vL64eE5WTEjeSKHYCTkt5QagV53sXpKTFlTHRQsrcr_eIt2GMqUR6Q6n7SFO2Y7FY7YF6cWPS073Oeyw0KmSaHM80E3wtY7jFOwU0kiTpz7FGNwcbaZbjHvMdE0dxljoZs5hvKbWzRPS25BtpGH06JbOV-SFt7Hg64f7jKy_XKzPL5ur71-_nX--alwnYWp0vYRj3DrQYNmglByUbZmUcug06B5ADxa04FpycF5L1Aw9DloBCN-ekU9H2f087HDj6uZ1DbP4svlgkg3m78oYtuY63RoJPWeiqwLvHwRy-jljmcwulMWeHTHNxXCmVJ2ltKjou3_QmzTnsbozvBVa9X2v2kqxI-VyKiWjf1qGgVmyNcdsTc3WLNmau9rz9k8XTx2PYVaAH4GyX74c8-_R_1f9BfGjscs</recordid><startdate>20200301</startdate><enddate>20200301</enddate><creator>Chen, Xiangyu</creator><creator>Cao, Guoshuai</creator><creator>Wu, Jialin</creator><creator>Wang, Xinxin</creator><creator>Pan, Zhiwei</creator><creator>Gao, Jianbao</creator><creator>Tian, Qin</creator><creator>Xu, Lifan</creator><creator>Li, Zhirong</creator><creator>Hao, Yaxing</creator><creator>Huang, Qizhao</creator><creator>Wang, Pengcheng</creator><creator>Xiao, Minglu</creator><creator>Xie, Luoyingzi</creator><creator>Tang, Shupei</creator><creator>Liu, Zhenyu</creator><creator>Hu, Li</creator><creator>Tang, Jianfang</creator><creator>He, Ran</creator><creator>Wang, Li</creator><creator>Zhou, Xinyuan</creator><creator>Wu, Yuzhang</creator><creator>Chen, Mengjie</creator><creator>Sun, Beicheng</creator><creator>Zhu, Bo</creator><creator>Huang, Jun</creator><creator>Ye, Lilin</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-0778-3311</orcidid></search><sort><creationdate>20200301</creationdate><title>The histone methyltransferase EZH2 primes the early differentiation of follicular helper T cells during acute viral infection</title><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></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c470t-9c476c12ac090a1b887b8a31777b49095009ba09629720cf97e91efeb98006f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>631/250/2152/1566/2493</topic><topic>631/250/2499</topic><topic>631/250/254</topic><topic>Antibodies</topic><topic>Bcl-6 protein</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>CD4 antigen</topic><topic>Cell differentiation</topic><topic>Cell fate</topic><topic>Chromatin</topic><topic>Effector cells</topic><topic>Histone methyltransferase</topic><topic>Histones</topic><topic>Immunology</topic><topic>Infections</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Medical Microbiology</topic><topic>Microbiology</topic><topic>Vaccine</topic><topic>Viral infections</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Xiangyu</creatorcontrib><creatorcontrib>Cao, Guoshuai</creatorcontrib><creatorcontrib>Wu, Jialin</creatorcontrib><creatorcontrib>Wang, Xinxin</creatorcontrib><creatorcontrib>Pan, Zhiwei</creatorcontrib><creatorcontrib>Gao, Jianbao</creatorcontrib><creatorcontrib>Tian, Qin</creatorcontrib><creatorcontrib>Xu, Lifan</creatorcontrib><creatorcontrib>Li, Zhirong</creatorcontrib><creatorcontrib>Hao, Yaxing</creatorcontrib><creatorcontrib>Huang, Qizhao</creatorcontrib><creatorcontrib>Wang, Pengcheng</creatorcontrib><creatorcontrib>Xiao, Minglu</creatorcontrib><creatorcontrib>Xie, Luoyingzi</creatorcontrib><creatorcontrib>Tang, Shupei</creatorcontrib><creatorcontrib>Liu, Zhenyu</creatorcontrib><creatorcontrib>Hu, Li</creatorcontrib><creatorcontrib>Tang, Jianfang</creatorcontrib><creatorcontrib>He, Ran</creatorcontrib><creatorcontrib>Wang, Li</creatorcontrib><creatorcontrib>Zhou, Xinyuan</creatorcontrib><creatorcontrib>Wu, Yuzhang</creatorcontrib><creatorcontrib>Chen, Mengjie</creatorcontrib><creatorcontrib>Sun, Beicheng</creatorcontrib><creatorcontrib>Zhu, Bo</creatorcontrib><creatorcontrib>Huang, Jun</creatorcontrib><creatorcontrib>Ye, Lilin</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection (ProQuest)</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cellular & molecular immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Xiangyu</au><au>Cao, Guoshuai</au><au>Wu, Jialin</au><au>Wang, Xinxin</au><au>Pan, Zhiwei</au><au>Gao, Jianbao</au><au>Tian, Qin</au><au>Xu, Lifan</au><au>Li, Zhirong</au><au>Hao, Yaxing</au><au>Huang, Qizhao</au><au>Wang, Pengcheng</au><au>Xiao, Minglu</au><au>Xie, Luoyingzi</au><au>Tang, Shupei</au><au>Liu, Zhenyu</au><au>Hu, Li</au><au>Tang, Jianfang</au><au>He, Ran</au><au>Wang, Li</au><au>Zhou, Xinyuan</au><au>Wu, Yuzhang</au><au>Chen, Mengjie</au><au>Sun, Beicheng</au><au>Zhu, Bo</au><au>Huang, Jun</au><au>Ye, Lilin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The histone methyltransferase EZH2 primes the early differentiation of follicular helper T cells during acute viral infection</atitle><jtitle>Cellular & molecular immunology</jtitle><stitle>Cell Mol Immunol</stitle><addtitle>Cell Mol Immunol</addtitle><date>2020-03-01</date><risdate>2020</risdate><volume>17</volume><issue>3</issue><spage>247</spage><epage>260</epage><pages>247-260</pages><issn>1672-7681</issn><eissn>2042-0226</eissn><abstract>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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>30842630</pmid><doi>10.1038/s41423-019-0219-z</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0003-0778-3311</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1672-7681 |
| ispartof | Cellular & molecular immunology, 2020-03, Vol.17 (3), p.247-260 |
| issn | 1672-7681 2042-0226 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7052164 |
| source | EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection |
| subjects | 631/250/2152/1566/2493 631/250/2499 631/250/254 Antibodies Bcl-6 protein Biomedical and Life Sciences Biomedicine CD4 antigen Cell differentiation Cell fate Chromatin Effector cells Histone methyltransferase Histones Immunology Infections Lymphocytes Lymphocytes T Medical Microbiology Microbiology Vaccine Viral infections |
| title | The histone methyltransferase EZH2 primes the early differentiation of follicular helper T cells during acute viral infection |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-16T05%3A59%3A03IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20histone%20methyltransferase%20EZH2%20primes%20the%20early%20differentiation%20of%20follicular%20helper%20T%20cells%20during%20acute%20viral%20infection&rft.jtitle=Cellular%20&%20molecular%20immunology&rft.au=Chen,%20Xiangyu&rft.date=2020-03-01&rft.volume=17&rft.issue=3&rft.spage=247&rft.epage=260&rft.pages=247-260&rft.issn=1672-7681&rft.eissn=2042-0226&rft_id=info:doi/10.1038/s41423-019-0219-z&rft_dat=%3Cproquest_pubme%3E2369855583%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2369855583&rft_id=info:pmid/30842630&rfr_iscdi=true |