T-cell expression of AhR inhibits the maintenance of pT reg cells in the gastrointestinal tract in acute GVHD
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that affects the function and development of immune cells. Here, we show that recipient mice receiving AhR T cells have improved survival and decreased acute graft-versus-host disease (aGVHD) in 2 different murine allogen...
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| Veröffentlicht in: | Blood 2017-07, Vol.130 (3), p.348 |
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| creator | Dant, Trisha A Lin, Kaifeng L Bruce, Danny W Montgomery, Stephanie A Kolupaev, Oleg V Bommiasamy, Hemamalini Bixby, Lisa M Woosley, John T McKinnon, Karen P Gonzalez, Frank J Blazar, Bruce R Vincent, Benjamin G Coghill, James M Serody, Jonathan S |
| description | The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that affects the function and development of immune cells. Here, we show that recipient mice receiving AhR
T cells have improved survival and decreased acute graft-versus-host disease (aGVHD) in 2 different murine allogeneic bone marrow transplant (BMT) models. We also show that CD4
T cells lacking AhR demonstrate reduced accumulation in secondary lymphoid tissue because of low levels of proliferation 4 days after BMT. Additionally, we found a significant increase in the quantity of peripherally induced regulatory donor T (pT
) cells in the colon of recipients transplanted with AhR
T cells 14 days after transplant. Blockade of AhR using a clinically available AhR antagonist greatly enhanced the in vitro generation of inducible T
(iT
) cells from naïve CD4
human T cells. We have identified AhR as a novel target on donor T cells that is critical to the pathogenesis of aGVHD. |
| format | Article |
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T cells have improved survival and decreased acute graft-versus-host disease (aGVHD) in 2 different murine allogeneic bone marrow transplant (BMT) models. We also show that CD4
T cells lacking AhR demonstrate reduced accumulation in secondary lymphoid tissue because of low levels of proliferation 4 days after BMT. Additionally, we found a significant increase in the quantity of peripherally induced regulatory donor T (pT
) cells in the colon of recipients transplanted with AhR
T cells 14 days after transplant. Blockade of AhR using a clinically available AhR antagonist greatly enhanced the in vitro generation of inducible T
(iT
) cells from naïve CD4
human T cells. We have identified AhR as a novel target on donor T cells that is critical to the pathogenesis of aGVHD.</description><identifier>EISSN: 1528-0020</identifier><identifier>PMID: 28550042</identifier><language>eng</language><publisher>United States</publisher><subject>Acute Disease ; Animals ; Basic Helix-Loop-Helix Transcription Factors - deficiency ; Basic Helix-Loop-Helix Transcription Factors - genetics ; Basic Helix-Loop-Helix Transcription Factors - immunology ; Bone Marrow Transplantation ; Cell Proliferation ; Colon - immunology ; Colon - pathology ; Gene Expression Regulation ; Graft vs Host Disease - immunology ; Graft vs Host Disease - mortality ; Graft vs Host Disease - pathology ; Graft vs Host Disease - prevention & control ; Humans ; Lymphocyte Activation ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Purines - pharmacology ; Receptors, Aryl Hydrocarbon - deficiency ; Receptors, Aryl Hydrocarbon - genetics ; Receptors, Aryl Hydrocarbon - immunology ; Sirolimus - pharmacology ; Survival Analysis ; T-Lymphocytes, Regulatory - cytology ; T-Lymphocytes, Regulatory - drug effects ; T-Lymphocytes, Regulatory - immunology ; T-Lymphocytes, Regulatory - transplantation ; Transplantation, Heterologous</subject><ispartof>Blood, 2017-07, Vol.130 (3), p.348</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><orcidid>0000-0003-4568-1092</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,782,786</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28550042$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dant, Trisha A</creatorcontrib><creatorcontrib>Lin, Kaifeng L</creatorcontrib><creatorcontrib>Bruce, Danny W</creatorcontrib><creatorcontrib>Montgomery, Stephanie A</creatorcontrib><creatorcontrib>Kolupaev, Oleg V</creatorcontrib><creatorcontrib>Bommiasamy, Hemamalini</creatorcontrib><creatorcontrib>Bixby, Lisa M</creatorcontrib><creatorcontrib>Woosley, John T</creatorcontrib><creatorcontrib>McKinnon, Karen P</creatorcontrib><creatorcontrib>Gonzalez, Frank J</creatorcontrib><creatorcontrib>Blazar, Bruce R</creatorcontrib><creatorcontrib>Vincent, Benjamin G</creatorcontrib><creatorcontrib>Coghill, James M</creatorcontrib><creatorcontrib>Serody, Jonathan S</creatorcontrib><title>T-cell expression of AhR inhibits the maintenance of pT reg cells in the gastrointestinal tract in acute GVHD</title><title>Blood</title><addtitle>Blood</addtitle><description>The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that affects the function and development of immune cells. Here, we show that recipient mice receiving AhR
T cells have improved survival and decreased acute graft-versus-host disease (aGVHD) in 2 different murine allogeneic bone marrow transplant (BMT) models. We also show that CD4
T cells lacking AhR demonstrate reduced accumulation in secondary lymphoid tissue because of low levels of proliferation 4 days after BMT. Additionally, we found a significant increase in the quantity of peripherally induced regulatory donor T (pT
) cells in the colon of recipients transplanted with AhR
T cells 14 days after transplant. Blockade of AhR using a clinically available AhR antagonist greatly enhanced the in vitro generation of inducible T
(iT
) cells from naïve CD4
human T cells. We have identified AhR as a novel target on donor T cells that is critical to the pathogenesis of aGVHD.</description><subject>Acute Disease</subject><subject>Animals</subject><subject>Basic Helix-Loop-Helix Transcription Factors - deficiency</subject><subject>Basic Helix-Loop-Helix Transcription Factors - genetics</subject><subject>Basic Helix-Loop-Helix Transcription Factors - immunology</subject><subject>Bone Marrow Transplantation</subject><subject>Cell Proliferation</subject><subject>Colon - immunology</subject><subject>Colon - pathology</subject><subject>Gene Expression Regulation</subject><subject>Graft vs Host Disease - immunology</subject><subject>Graft vs Host Disease - mortality</subject><subject>Graft vs Host Disease - pathology</subject><subject>Graft vs Host Disease - prevention & control</subject><subject>Humans</subject><subject>Lymphocyte Activation</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Purines - pharmacology</subject><subject>Receptors, Aryl Hydrocarbon - deficiency</subject><subject>Receptors, Aryl Hydrocarbon - genetics</subject><subject>Receptors, Aryl Hydrocarbon - immunology</subject><subject>Sirolimus - pharmacology</subject><subject>Survival Analysis</subject><subject>T-Lymphocytes, Regulatory - cytology</subject><subject>T-Lymphocytes, Regulatory - drug effects</subject><subject>T-Lymphocytes, Regulatory - immunology</subject><subject>T-Lymphocytes, Regulatory - transplantation</subject><subject>Transplantation, Heterologous</subject><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFzs0KgkAUBeAhiLSfV4j7AsI4KriN_lyHtJVxuuqEjjJ3hHr7Mmrd6izOd-DMmB8mIg04F9xjS6I752EciWTBPJEmCeex8FmXBwrbFvAxWCTSvYG-gl1zAW0aXWpH4BqETmrj0EijcOqHHCzWMC3pDT-kluRsPzFy2sgWnJXKTa1Uo0M4X7PDms0r2RJuvrli29Mx32fBMJYd3orB6k7aZ_H7F_0FL2RTRfg</recordid><startdate>20170720</startdate><enddate>20170720</enddate><creator>Dant, Trisha A</creator><creator>Lin, Kaifeng L</creator><creator>Bruce, Danny W</creator><creator>Montgomery, Stephanie A</creator><creator>Kolupaev, Oleg V</creator><creator>Bommiasamy, Hemamalini</creator><creator>Bixby, Lisa M</creator><creator>Woosley, John T</creator><creator>McKinnon, Karen P</creator><creator>Gonzalez, Frank J</creator><creator>Blazar, Bruce R</creator><creator>Vincent, Benjamin G</creator><creator>Coghill, James M</creator><creator>Serody, Jonathan S</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><orcidid>https://orcid.org/0000-0003-4568-1092</orcidid></search><sort><creationdate>20170720</creationdate><title>T-cell expression of AhR inhibits the maintenance of pT reg cells in the gastrointestinal tract in acute GVHD</title><author>Dant, Trisha A ; Lin, Kaifeng L ; Bruce, Danny W ; Montgomery, Stephanie A ; Kolupaev, Oleg V ; Bommiasamy, Hemamalini ; Bixby, Lisa M ; Woosley, John T ; McKinnon, Karen P ; Gonzalez, Frank J ; Blazar, Bruce R ; Vincent, Benjamin G ; Coghill, James M ; Serody, Jonathan S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-pubmed_primary_285500423</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Acute Disease</topic><topic>Animals</topic><topic>Basic Helix-Loop-Helix Transcription Factors - deficiency</topic><topic>Basic Helix-Loop-Helix Transcription Factors - genetics</topic><topic>Basic Helix-Loop-Helix Transcription Factors - immunology</topic><topic>Bone Marrow Transplantation</topic><topic>Cell Proliferation</topic><topic>Colon - immunology</topic><topic>Colon - pathology</topic><topic>Gene Expression Regulation</topic><topic>Graft vs Host Disease - immunology</topic><topic>Graft vs Host Disease - mortality</topic><topic>Graft vs Host Disease - pathology</topic><topic>Graft vs Host Disease - prevention & control</topic><topic>Humans</topic><topic>Lymphocyte Activation</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Purines - pharmacology</topic><topic>Receptors, Aryl Hydrocarbon - deficiency</topic><topic>Receptors, Aryl Hydrocarbon - genetics</topic><topic>Receptors, Aryl Hydrocarbon - immunology</topic><topic>Sirolimus - pharmacology</topic><topic>Survival Analysis</topic><topic>T-Lymphocytes, Regulatory - cytology</topic><topic>T-Lymphocytes, Regulatory - drug effects</topic><topic>T-Lymphocytes, Regulatory - immunology</topic><topic>T-Lymphocytes, Regulatory - transplantation</topic><topic>Transplantation, Heterologous</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dant, Trisha A</creatorcontrib><creatorcontrib>Lin, Kaifeng L</creatorcontrib><creatorcontrib>Bruce, Danny W</creatorcontrib><creatorcontrib>Montgomery, Stephanie A</creatorcontrib><creatorcontrib>Kolupaev, Oleg V</creatorcontrib><creatorcontrib>Bommiasamy, Hemamalini</creatorcontrib><creatorcontrib>Bixby, Lisa M</creatorcontrib><creatorcontrib>Woosley, John T</creatorcontrib><creatorcontrib>McKinnon, Karen P</creatorcontrib><creatorcontrib>Gonzalez, Frank J</creatorcontrib><creatorcontrib>Blazar, Bruce R</creatorcontrib><creatorcontrib>Vincent, Benjamin G</creatorcontrib><creatorcontrib>Coghill, James M</creatorcontrib><creatorcontrib>Serody, Jonathan S</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dant, Trisha A</au><au>Lin, Kaifeng L</au><au>Bruce, Danny W</au><au>Montgomery, Stephanie A</au><au>Kolupaev, Oleg V</au><au>Bommiasamy, Hemamalini</au><au>Bixby, Lisa M</au><au>Woosley, John T</au><au>McKinnon, Karen P</au><au>Gonzalez, Frank J</au><au>Blazar, Bruce R</au><au>Vincent, Benjamin G</au><au>Coghill, James M</au><au>Serody, Jonathan S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>T-cell expression of AhR inhibits the maintenance of pT reg cells in the gastrointestinal tract in acute GVHD</atitle><jtitle>Blood</jtitle><addtitle>Blood</addtitle><date>2017-07-20</date><risdate>2017</risdate><volume>130</volume><issue>3</issue><spage>348</spage><pages>348-</pages><eissn>1528-0020</eissn><abstract>The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that affects the function and development of immune cells. Here, we show that recipient mice receiving AhR
T cells have improved survival and decreased acute graft-versus-host disease (aGVHD) in 2 different murine allogeneic bone marrow transplant (BMT) models. We also show that CD4
T cells lacking AhR demonstrate reduced accumulation in secondary lymphoid tissue because of low levels of proliferation 4 days after BMT. Additionally, we found a significant increase in the quantity of peripherally induced regulatory donor T (pT
) cells in the colon of recipients transplanted with AhR
T cells 14 days after transplant. Blockade of AhR using a clinically available AhR antagonist greatly enhanced the in vitro generation of inducible T
(iT
) cells from naïve CD4
human T cells. We have identified AhR as a novel target on donor T cells that is critical to the pathogenesis of aGVHD.</abstract><cop>United States</cop><pmid>28550042</pmid><orcidid>https://orcid.org/0000-0003-4568-1092</orcidid></addata></record> |
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| source | MEDLINE; Alma/SFX Local Collection; EZB Electronic Journals Library |
| subjects | Acute Disease Animals Basic Helix-Loop-Helix Transcription Factors - deficiency Basic Helix-Loop-Helix Transcription Factors - genetics Basic Helix-Loop-Helix Transcription Factors - immunology Bone Marrow Transplantation Cell Proliferation Colon - immunology Colon - pathology Gene Expression Regulation Graft vs Host Disease - immunology Graft vs Host Disease - mortality Graft vs Host Disease - pathology Graft vs Host Disease - prevention & control Humans Lymphocyte Activation Mice Mice, Inbred C57BL Mice, Knockout Purines - pharmacology Receptors, Aryl Hydrocarbon - deficiency Receptors, Aryl Hydrocarbon - genetics Receptors, Aryl Hydrocarbon - immunology Sirolimus - pharmacology Survival Analysis T-Lymphocytes, Regulatory - cytology T-Lymphocytes, Regulatory - drug effects T-Lymphocytes, Regulatory - immunology T-Lymphocytes, Regulatory - transplantation Transplantation, Heterologous |
| title | T-cell expression of AhR inhibits the maintenance of pT reg cells in the gastrointestinal tract in acute GVHD |
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