Liver-Derived TGF-β Maintains the Eomes hi Tbet lo Phenotype of Liver Resident Natural Killer Cells
The adult human liver hosts a complex repertoire of liver resident and transient natural killer (NK) cell populations with diverse phenotypes and functions. Liver resident NK cells are CD56 NK cells defined by a unique expression profile of transcription factors and cell surface markers (Eomes Tbet...
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Veröffentlicht in: | Frontiers in immunology 2019, Vol.10, p.1502 |
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description | The adult human liver hosts a complex repertoire of liver resident and transient natural killer (NK) cell populations with diverse phenotypes and functions. Liver resident NK cells are CD56
NK cells defined by a unique expression profile of transcription factors and cell surface markers (Eomes
Tbet
TIGIT
CD69
CXCR6
CD49e
). Despite extensive characterization of the phenotype of liver resident NK cells, it remains unclear how factors within the liver microenvironment induce and maintain this unique phenotype. In this study, we have explored the factors regulating the phenotype of liver resident NK cells. Isolation of healthy liver resident NK cells from donor liver perfusate and
culture results in the gradual loss of the characteristic Tbet
phenotype, with the cells increasing Tbet expression significantly at day 7. This phenotypic loss could be halted through the dose-dependent addition of liver conditioned media (LCM), generated from the
culture of liver biopsies from healthy organ donors. TGF-β, but not IL-10, replicated the Tbet suppressive effects of LCM in both liver resident and peripheral blood NK cells. Furthermore, blocking TGF-β receptor signaling using the inhibitor SB431542, reversed the effect of LCM treatment on liver resident NK cells, causing the loss of tissue resident Eomes
Tbet
phenotype. Our findings identify liver-derived TGF-β as an important component of the liver microenvironment, which acts to regulate and maintain the phenotype of liver resident NK cells. |
format | Article |
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NK cells defined by a unique expression profile of transcription factors and cell surface markers (Eomes
Tbet
TIGIT
CD69
CXCR6
CD49e
). Despite extensive characterization of the phenotype of liver resident NK cells, it remains unclear how factors within the liver microenvironment induce and maintain this unique phenotype. In this study, we have explored the factors regulating the phenotype of liver resident NK cells. Isolation of healthy liver resident NK cells from donor liver perfusate and
culture results in the gradual loss of the characteristic Tbet
phenotype, with the cells increasing Tbet expression significantly at day 7. This phenotypic loss could be halted through the dose-dependent addition of liver conditioned media (LCM), generated from the
culture of liver biopsies from healthy organ donors. TGF-β, but not IL-10, replicated the Tbet suppressive effects of LCM in both liver resident and peripheral blood NK cells. Furthermore, blocking TGF-β receptor signaling using the inhibitor SB431542, reversed the effect of LCM treatment on liver resident NK cells, causing the loss of tissue resident Eomes
Tbet
phenotype. Our findings identify liver-derived TGF-β as an important component of the liver microenvironment, which acts to regulate and maintain the phenotype of liver resident NK cells.</description><identifier>EISSN: 1664-3224</identifier><identifier>PMID: 31333651</identifier><language>eng</language><publisher>Switzerland</publisher><ispartof>Frontiers in immunology, 2019, Vol.10, p.1502</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,4024</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31333651$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Harmon, Cathal</creatorcontrib><creatorcontrib>Jameson, Gráinne</creatorcontrib><creatorcontrib>Almuaili, Dalal</creatorcontrib><creatorcontrib>Houlihan, Diarmaid D</creatorcontrib><creatorcontrib>Hoti, Emir</creatorcontrib><creatorcontrib>Geoghegan, Justin</creatorcontrib><creatorcontrib>Robinson, Mark W</creatorcontrib><creatorcontrib>O'Farrelly, Cliona</creatorcontrib><title>Liver-Derived TGF-β Maintains the Eomes hi Tbet lo Phenotype of Liver Resident Natural Killer Cells</title><title>Frontiers in immunology</title><addtitle>Front Immunol</addtitle><description>The adult human liver hosts a complex repertoire of liver resident and transient natural killer (NK) cell populations with diverse phenotypes and functions. Liver resident NK cells are CD56
NK cells defined by a unique expression profile of transcription factors and cell surface markers (Eomes
Tbet
TIGIT
CD69
CXCR6
CD49e
). Despite extensive characterization of the phenotype of liver resident NK cells, it remains unclear how factors within the liver microenvironment induce and maintain this unique phenotype. In this study, we have explored the factors regulating the phenotype of liver resident NK cells. Isolation of healthy liver resident NK cells from donor liver perfusate and
culture results in the gradual loss of the characteristic Tbet
phenotype, with the cells increasing Tbet expression significantly at day 7. This phenotypic loss could be halted through the dose-dependent addition of liver conditioned media (LCM), generated from the
culture of liver biopsies from healthy organ donors. TGF-β, but not IL-10, replicated the Tbet suppressive effects of LCM in both liver resident and peripheral blood NK cells. Furthermore, blocking TGF-β receptor signaling using the inhibitor SB431542, reversed the effect of LCM treatment on liver resident NK cells, causing the loss of tissue resident Eomes
Tbet
phenotype. Our findings identify liver-derived TGF-β as an important component of the liver microenvironment, which acts to regulate and maintain the phenotype of liver resident NK cells.</description><issn>1664-3224</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNqFTl0KgkAYXIJIKa8Q3wWEdFXo2bSgHyJ8l5X9xI31h9018FodpDO1RD03MMwwDMPMiBskSeTTMIwc4ml931hEW0ppvCAODaxJ4sAl_CQeqPwdKqscin3uv55wZqIzlhpMg5D1LWpoBBQVGpA9XBvsejMNCH0NnwG4oRYcOwMXZkbFJByFlDZPUUq9IvOaSY3eV5dknWdFevCHsWqRl4MSLVNT-btF_xbeWCtDcA</recordid><startdate>2019</startdate><enddate>2019</enddate><creator>Harmon, Cathal</creator><creator>Jameson, Gráinne</creator><creator>Almuaili, Dalal</creator><creator>Houlihan, Diarmaid D</creator><creator>Hoti, Emir</creator><creator>Geoghegan, Justin</creator><creator>Robinson, Mark W</creator><creator>O'Farrelly, Cliona</creator><scope>NPM</scope></search><sort><creationdate>2019</creationdate><title>Liver-Derived TGF-β Maintains the Eomes hi Tbet lo Phenotype of Liver Resident Natural Killer Cells</title><author>Harmon, Cathal ; Jameson, Gráinne ; Almuaili, Dalal ; Houlihan, Diarmaid D ; Hoti, Emir ; Geoghegan, Justin ; Robinson, Mark W ; O'Farrelly, Cliona</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-pubmed_primary_313336513</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Harmon, Cathal</creatorcontrib><creatorcontrib>Jameson, Gráinne</creatorcontrib><creatorcontrib>Almuaili, Dalal</creatorcontrib><creatorcontrib>Houlihan, Diarmaid D</creatorcontrib><creatorcontrib>Hoti, Emir</creatorcontrib><creatorcontrib>Geoghegan, Justin</creatorcontrib><creatorcontrib>Robinson, Mark W</creatorcontrib><creatorcontrib>O'Farrelly, Cliona</creatorcontrib><collection>PubMed</collection><jtitle>Frontiers in immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Harmon, Cathal</au><au>Jameson, Gráinne</au><au>Almuaili, Dalal</au><au>Houlihan, Diarmaid D</au><au>Hoti, Emir</au><au>Geoghegan, Justin</au><au>Robinson, Mark W</au><au>O'Farrelly, Cliona</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Liver-Derived TGF-β Maintains the Eomes hi Tbet lo Phenotype of Liver Resident Natural Killer Cells</atitle><jtitle>Frontiers in immunology</jtitle><addtitle>Front Immunol</addtitle><date>2019</date><risdate>2019</risdate><volume>10</volume><spage>1502</spage><pages>1502-</pages><eissn>1664-3224</eissn><abstract>The adult human liver hosts a complex repertoire of liver resident and transient natural killer (NK) cell populations with diverse phenotypes and functions. Liver resident NK cells are CD56
NK cells defined by a unique expression profile of transcription factors and cell surface markers (Eomes
Tbet
TIGIT
CD69
CXCR6
CD49e
). Despite extensive characterization of the phenotype of liver resident NK cells, it remains unclear how factors within the liver microenvironment induce and maintain this unique phenotype. In this study, we have explored the factors regulating the phenotype of liver resident NK cells. Isolation of healthy liver resident NK cells from donor liver perfusate and
culture results in the gradual loss of the characteristic Tbet
phenotype, with the cells increasing Tbet expression significantly at day 7. This phenotypic loss could be halted through the dose-dependent addition of liver conditioned media (LCM), generated from the
culture of liver biopsies from healthy organ donors. TGF-β, but not IL-10, replicated the Tbet suppressive effects of LCM in both liver resident and peripheral blood NK cells. Furthermore, blocking TGF-β receptor signaling using the inhibitor SB431542, reversed the effect of LCM treatment on liver resident NK cells, causing the loss of tissue resident Eomes
Tbet
phenotype. Our findings identify liver-derived TGF-β as an important component of the liver microenvironment, which acts to regulate and maintain the phenotype of liver resident NK cells.</abstract><cop>Switzerland</cop><pmid>31333651</pmid></addata></record> |
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source | DOAJ Directory of Open Access Journals; PubMed Central Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central |
title | Liver-Derived TGF-β Maintains the Eomes hi Tbet lo Phenotype of Liver Resident Natural Killer Cells |
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