Id2-mediated inhibition of E2A represses memory CD8+ T cell differentiation
The transcription factor inhibitor of DNA binding (Id)2 modulates T cell fate decisions, but the molecular mechanism underpinning this regulation is unclear. In this study we show that loss of Id2 cripples effector differentiation and instead programs CD8(+) T cells to adopt a memory fate with incre...
Gespeichert in:
| Veröffentlicht in: | The Journal of immunology (1950) 2013-05, Vol.190 (9), p.4585-4594 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 4594 |
|---|---|
| container_issue | 9 |
| container_start_page | 4585 |
| container_title | The Journal of immunology (1950) |
| container_volume | 190 |
| creator | Masson, Frederick Minnich, Martina Olshansky, Moshe Bilic, Ivan Mount, Adele M Kallies, Axel Speed, Terence P Busslinger, Meinrad Nutt, Stephen L Belz, Gabrielle T |
| description | The transcription factor inhibitor of DNA binding (Id)2 modulates T cell fate decisions, but the molecular mechanism underpinning this regulation is unclear. In this study we show that loss of Id2 cripples effector differentiation and instead programs CD8(+) T cells to adopt a memory fate with increased Eomesodermin and Tcf7 expression. We demonstrate that Id2 restrains CD8(+) T cell memory differentiation by inhibiting E2A-mediated direct activation of Tcf7 and that Id2 expression level mirrors T cell memory recall capacity. As a result of the defective effector differentiation, Id2-deficient CD8(+) T cells fail to induce sufficient Tbx21 expression to generate short-lived effector CD8(+) T cells. Our findings reveal that the Id2/E2A axis orchestrates T cell differentiation through the induction or repression of downstream transcription factors essential for effector and memory T cell differentiation. |
| doi_str_mv | 10.4049/jimmunol.1300099 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3631715</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1551629926</sourcerecordid><originalsourceid>FETCH-LOGICAL-c463t-e596eb5eca47b778183a405f9be8eecce4ee96004f016eec6f186db449bdb7f13</originalsourceid><addsrcrecordid>eNqFUU1rGzEUFKUhdt3ceyo6NpRNnj5Wu7oUjJsmIYZc0rPYj6daYXflSmuD_31l7Jgml5wETzPzZt4Q8oXBlQSpr59d328G310xAQBafyBTlueQKQXqI5kCcJ6xQhUT8inG5wRRwOU5mXCRC6W4npKH-5ZnPbauGrGlbli52o3OD9RbesPnNOA6YIwYaY-9Dzu6-Fl-p0-0wa6jrbMWAw5jYifOZ3Jmqy7ixfGdkd-_bp4Wd9ny8fZ-MV9mjVRizDDXCuscm0oWdVGUrBSVhNzqGkvEpkGJqBWAtMBUGijLStXWUuq6rQvLxIz8OOiuN3Wy3iQDoerMOri-CjvjK2de_wxuZf74rRFKsILlSeDyILB6Q7ubL81-BlyU6Tx8u1_27bgs-L8bjKPpXdynrwb0m2jSvVmCaq7ehwpRCp3LFHhG4ABtgo8xoD3ZYGD21ZqXas2x2kT5-n_qE-GlS_EPJgChCA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1338395418</pqid></control><display><type>article</type><title>Id2-mediated inhibition of E2A represses memory CD8+ T cell differentiation</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Masson, Frederick ; Minnich, Martina ; Olshansky, Moshe ; Bilic, Ivan ; Mount, Adele M ; Kallies, Axel ; Speed, Terence P ; Busslinger, Meinrad ; Nutt, Stephen L ; Belz, Gabrielle T</creator><creatorcontrib>Masson, Frederick ; Minnich, Martina ; Olshansky, Moshe ; Bilic, Ivan ; Mount, Adele M ; Kallies, Axel ; Speed, Terence P ; Busslinger, Meinrad ; Nutt, Stephen L ; Belz, Gabrielle T</creatorcontrib><description>The transcription factor inhibitor of DNA binding (Id)2 modulates T cell fate decisions, but the molecular mechanism underpinning this regulation is unclear. In this study we show that loss of Id2 cripples effector differentiation and instead programs CD8(+) T cells to adopt a memory fate with increased Eomesodermin and Tcf7 expression. We demonstrate that Id2 restrains CD8(+) T cell memory differentiation by inhibiting E2A-mediated direct activation of Tcf7 and that Id2 expression level mirrors T cell memory recall capacity. As a result of the defective effector differentiation, Id2-deficient CD8(+) T cells fail to induce sufficient Tbx21 expression to generate short-lived effector CD8(+) T cells. Our findings reveal that the Id2/E2A axis orchestrates T cell differentiation through the induction or repression of downstream transcription factors essential for effector and memory T cell differentiation.</description><identifier>ISSN: 0022-1767</identifier><identifier>ISSN: 1550-6606</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.1300099</identifier><identifier>PMID: 23536629</identifier><language>eng</language><publisher>United States: Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists</publisher><subject>Animals ; Basic Helix-Loop-Helix Transcription Factors - antagonists & inhibitors ; Basic Helix-Loop-Helix Transcription Factors - genetics ; Basic Helix-Loop-Helix Transcription Factors - immunology ; Basic Helix-Loop-Helix Transcription Factors - metabolism ; CD8-Positive T-Lymphocytes - cytology ; CD8-Positive T-Lymphocytes - immunology ; CD8-Positive T-Lymphocytes - metabolism ; Cell Differentiation - genetics ; Cell Differentiation - immunology ; Gene Expression - immunology ; Hepatocyte Nuclear Factor 1-alpha ; Immune Regulation ; Immunologic Memory - genetics ; Immunologic Memory - immunology ; Inhibitor of Differentiation Protein 2 - genetics ; Inhibitor of Differentiation Protein 2 - immunology ; Inhibitor of Differentiation Protein 2 - metabolism ; Life Sciences ; Mice ; Mice, Inbred C57BL ; T Cell Transcription Factor 1 - genetics ; T Cell Transcription Factor 1 - immunology ; T Cell Transcription Factor 1 - metabolism ; T-Box Domain Proteins - genetics ; T-Box Domain Proteins - immunology ; T-Box Domain Proteins - metabolism</subject><ispartof>The Journal of immunology (1950), 2013-05, Vol.190 (9), p.4585-4594</ispartof><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>Copyright © 2013 by The American Association of Immunologists, Inc. 2013 Copyright © 2013 by The American Association of Immunologists, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c463t-e596eb5eca47b778183a405f9be8eecce4ee96004f016eec6f186db449bdb7f13</citedby><cites>FETCH-LOGICAL-c463t-e596eb5eca47b778183a405f9be8eecce4ee96004f016eec6f186db449bdb7f13</cites><orcidid>0000-0002-0020-6637 ; 0000-0002-9660-9587 ; 0000-0001-9909-2985</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23536629$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-02386292$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Masson, Frederick</creatorcontrib><creatorcontrib>Minnich, Martina</creatorcontrib><creatorcontrib>Olshansky, Moshe</creatorcontrib><creatorcontrib>Bilic, Ivan</creatorcontrib><creatorcontrib>Mount, Adele M</creatorcontrib><creatorcontrib>Kallies, Axel</creatorcontrib><creatorcontrib>Speed, Terence P</creatorcontrib><creatorcontrib>Busslinger, Meinrad</creatorcontrib><creatorcontrib>Nutt, Stephen L</creatorcontrib><creatorcontrib>Belz, Gabrielle T</creatorcontrib><title>Id2-mediated inhibition of E2A represses memory CD8+ T cell differentiation</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>The transcription factor inhibitor of DNA binding (Id)2 modulates T cell fate decisions, but the molecular mechanism underpinning this regulation is unclear. In this study we show that loss of Id2 cripples effector differentiation and instead programs CD8(+) T cells to adopt a memory fate with increased Eomesodermin and Tcf7 expression. We demonstrate that Id2 restrains CD8(+) T cell memory differentiation by inhibiting E2A-mediated direct activation of Tcf7 and that Id2 expression level mirrors T cell memory recall capacity. As a result of the defective effector differentiation, Id2-deficient CD8(+) T cells fail to induce sufficient Tbx21 expression to generate short-lived effector CD8(+) T cells. Our findings reveal that the Id2/E2A axis orchestrates T cell differentiation through the induction or repression of downstream transcription factors essential for effector and memory T cell differentiation.</description><subject>Animals</subject><subject>Basic Helix-Loop-Helix Transcription Factors - antagonists & inhibitors</subject><subject>Basic Helix-Loop-Helix Transcription Factors - genetics</subject><subject>Basic Helix-Loop-Helix Transcription Factors - immunology</subject><subject>Basic Helix-Loop-Helix Transcription Factors - metabolism</subject><subject>CD8-Positive T-Lymphocytes - cytology</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>CD8-Positive T-Lymphocytes - metabolism</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Differentiation - immunology</subject><subject>Gene Expression - immunology</subject><subject>Hepatocyte Nuclear Factor 1-alpha</subject><subject>Immune Regulation</subject><subject>Immunologic Memory - genetics</subject><subject>Immunologic Memory - immunology</subject><subject>Inhibitor of Differentiation Protein 2 - genetics</subject><subject>Inhibitor of Differentiation Protein 2 - immunology</subject><subject>Inhibitor of Differentiation Protein 2 - metabolism</subject><subject>Life Sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>T Cell Transcription Factor 1 - genetics</subject><subject>T Cell Transcription Factor 1 - immunology</subject><subject>T Cell Transcription Factor 1 - metabolism</subject><subject>T-Box Domain Proteins - genetics</subject><subject>T-Box Domain Proteins - immunology</subject><subject>T-Box Domain Proteins - metabolism</subject><issn>0022-1767</issn><issn>1550-6606</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUU1rGzEUFKUhdt3ceyo6NpRNnj5Wu7oUjJsmIYZc0rPYj6daYXflSmuD_31l7Jgml5wETzPzZt4Q8oXBlQSpr59d328G310xAQBafyBTlueQKQXqI5kCcJ6xQhUT8inG5wRRwOU5mXCRC6W4npKH-5ZnPbauGrGlbli52o3OD9RbesPnNOA6YIwYaY-9Dzu6-Fl-p0-0wa6jrbMWAw5jYifOZ3Jmqy7ixfGdkd-_bp4Wd9ny8fZ-MV9mjVRizDDXCuscm0oWdVGUrBSVhNzqGkvEpkGJqBWAtMBUGijLStXWUuq6rQvLxIz8OOiuN3Wy3iQDoerMOri-CjvjK2de_wxuZf74rRFKsILlSeDyILB6Q7ubL81-BlyU6Tx8u1_27bgs-L8bjKPpXdynrwb0m2jSvVmCaq7ehwpRCp3LFHhG4ABtgo8xoD3ZYGD21ZqXas2x2kT5-n_qE-GlS_EPJgChCA</recordid><startdate>20130501</startdate><enddate>20130501</enddate><creator>Masson, Frederick</creator><creator>Minnich, Martina</creator><creator>Olshansky, Moshe</creator><creator>Bilic, Ivan</creator><creator>Mount, Adele M</creator><creator>Kallies, Axel</creator><creator>Speed, Terence P</creator><creator>Busslinger, Meinrad</creator><creator>Nutt, Stephen L</creator><creator>Belz, Gabrielle T</creator><general>Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists</general><general>AAI</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7T5</scope><scope>H94</scope><scope>1XC</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-0020-6637</orcidid><orcidid>https://orcid.org/0000-0002-9660-9587</orcidid><orcidid>https://orcid.org/0000-0001-9909-2985</orcidid></search><sort><creationdate>20130501</creationdate><title>Id2-mediated inhibition of E2A represses memory CD8+ T cell differentiation</title><author>Masson, Frederick ; Minnich, Martina ; Olshansky, Moshe ; Bilic, Ivan ; Mount, Adele M ; Kallies, Axel ; Speed, Terence P ; Busslinger, Meinrad ; Nutt, Stephen L ; Belz, Gabrielle T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c463t-e596eb5eca47b778183a405f9be8eecce4ee96004f016eec6f186db449bdb7f13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Basic Helix-Loop-Helix Transcription Factors - antagonists & inhibitors</topic><topic>Basic Helix-Loop-Helix Transcription Factors - genetics</topic><topic>Basic Helix-Loop-Helix Transcription Factors - immunology</topic><topic>Basic Helix-Loop-Helix Transcription Factors - metabolism</topic><topic>CD8-Positive T-Lymphocytes - cytology</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>CD8-Positive T-Lymphocytes - metabolism</topic><topic>Cell Differentiation - genetics</topic><topic>Cell Differentiation - immunology</topic><topic>Gene Expression - immunology</topic><topic>Hepatocyte Nuclear Factor 1-alpha</topic><topic>Immune Regulation</topic><topic>Immunologic Memory - genetics</topic><topic>Immunologic Memory - immunology</topic><topic>Inhibitor of Differentiation Protein 2 - genetics</topic><topic>Inhibitor of Differentiation Protein 2 - immunology</topic><topic>Inhibitor of Differentiation Protein 2 - metabolism</topic><topic>Life Sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>T Cell Transcription Factor 1 - genetics</topic><topic>T Cell Transcription Factor 1 - immunology</topic><topic>T Cell Transcription Factor 1 - metabolism</topic><topic>T-Box Domain Proteins - genetics</topic><topic>T-Box Domain Proteins - immunology</topic><topic>T-Box Domain Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Masson, Frederick</creatorcontrib><creatorcontrib>Minnich, Martina</creatorcontrib><creatorcontrib>Olshansky, Moshe</creatorcontrib><creatorcontrib>Bilic, Ivan</creatorcontrib><creatorcontrib>Mount, Adele M</creatorcontrib><creatorcontrib>Kallies, Axel</creatorcontrib><creatorcontrib>Speed, Terence P</creatorcontrib><creatorcontrib>Busslinger, Meinrad</creatorcontrib><creatorcontrib>Nutt, Stephen L</creatorcontrib><creatorcontrib>Belz, Gabrielle T</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Masson, Frederick</au><au>Minnich, Martina</au><au>Olshansky, Moshe</au><au>Bilic, Ivan</au><au>Mount, Adele M</au><au>Kallies, Axel</au><au>Speed, Terence P</au><au>Busslinger, Meinrad</au><au>Nutt, Stephen L</au><au>Belz, Gabrielle T</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Id2-mediated inhibition of E2A represses memory CD8+ T cell differentiation</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2013-05-01</date><risdate>2013</risdate><volume>190</volume><issue>9</issue><spage>4585</spage><epage>4594</epage><pages>4585-4594</pages><issn>0022-1767</issn><issn>1550-6606</issn><eissn>1550-6606</eissn><abstract>The transcription factor inhibitor of DNA binding (Id)2 modulates T cell fate decisions, but the molecular mechanism underpinning this regulation is unclear. In this study we show that loss of Id2 cripples effector differentiation and instead programs CD8(+) T cells to adopt a memory fate with increased Eomesodermin and Tcf7 expression. We demonstrate that Id2 restrains CD8(+) T cell memory differentiation by inhibiting E2A-mediated direct activation of Tcf7 and that Id2 expression level mirrors T cell memory recall capacity. As a result of the defective effector differentiation, Id2-deficient CD8(+) T cells fail to induce sufficient Tbx21 expression to generate short-lived effector CD8(+) T cells. Our findings reveal that the Id2/E2A axis orchestrates T cell differentiation through the induction or repression of downstream transcription factors essential for effector and memory T cell differentiation.</abstract><cop>United States</cop><pub>Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists</pub><pmid>23536629</pmid><doi>10.4049/jimmunol.1300099</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-0020-6637</orcidid><orcidid>https://orcid.org/0000-0002-9660-9587</orcidid><orcidid>https://orcid.org/0000-0001-9909-2985</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-1767 |
| ispartof | The Journal of immunology (1950), 2013-05, Vol.190 (9), p.4585-4594 |
| issn | 0022-1767 1550-6606 1550-6606 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3631715 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Animals Basic Helix-Loop-Helix Transcription Factors - antagonists & inhibitors Basic Helix-Loop-Helix Transcription Factors - genetics Basic Helix-Loop-Helix Transcription Factors - immunology Basic Helix-Loop-Helix Transcription Factors - metabolism CD8-Positive T-Lymphocytes - cytology CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - metabolism Cell Differentiation - genetics Cell Differentiation - immunology Gene Expression - immunology Hepatocyte Nuclear Factor 1-alpha Immune Regulation Immunologic Memory - genetics Immunologic Memory - immunology Inhibitor of Differentiation Protein 2 - genetics Inhibitor of Differentiation Protein 2 - immunology Inhibitor of Differentiation Protein 2 - metabolism Life Sciences Mice Mice, Inbred C57BL T Cell Transcription Factor 1 - genetics T Cell Transcription Factor 1 - immunology T Cell Transcription Factor 1 - metabolism T-Box Domain Proteins - genetics T-Box Domain Proteins - immunology T-Box Domain Proteins - metabolism |
| title | Id2-mediated inhibition of E2A represses memory CD8+ T cell differentiation |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-13T15%3A41%3A37IST&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=Id2-mediated%20inhibition%20of%20E2A%20represses%20memory%20CD8+%20T%20cell%20differentiation&rft.jtitle=The%20Journal%20of%20immunology%20(1950)&rft.au=Masson,%20Frederick&rft.date=2013-05-01&rft.volume=190&rft.issue=9&rft.spage=4585&rft.epage=4594&rft.pages=4585-4594&rft.issn=0022-1767&rft.eissn=1550-6606&rft_id=info:doi/10.4049/jimmunol.1300099&rft_dat=%3Cproquest_pubme%3E1551629926%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=1338395418&rft_id=info:pmid/23536629&rfr_iscdi=true |