PTU-010 Role for GPR15 rather than beta 7 integrins in the pathogenesis of autoimmune liver disease
IntroductionG protein-coupled receptor 15 (GPR15) is a chemoattractant receptor that directs homing of lymphocytes to the colon. Furthermore, it has been shown to be a mediator of effector T cell homing during intestinal inflammation. Evidence exists showing infiltration of gut derived α4β7+ and CCR...
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| Veröffentlicht in: | Gut 2019-06, Vol.68 (Suppl 2), p.A116 |
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| description | IntroductionG protein-coupled receptor 15 (GPR15) is a chemoattractant receptor that directs homing of lymphocytes to the colon. Furthermore, it has been shown to be a mediator of effector T cell homing during intestinal inflammation. Evidence exists showing infiltration of gut derived α4β7+ and CCR9+ T cells in the hepatic infiltrate of patients with autoimmune liver disease (AILD), in particular primary sclerosing cholangitis (PSC), with expression of their complementary ligands also being identified on the hepatic endothelium. However, the role of GPR15 in hepatic gut T cell homing remains to be defined.MethodsExplanted liver tissue was collected from patients undergoing orthotopic liver transplantation for chronic liver disease (Alcoholic liver disease [ALD] n=3, Non-alcoholic fatty liver disease [NAFLD] n=3, PSC n=4) with healthy control tissue sourced from patients undergoing hepatocellular carcinoma (HCC) resection (n=4). Liver infiltrating lymphocytes (LIL) were isolated using a mechanical homogenisation and centrifugation/filtration technique. Expression of gut homing markers on T cells was quantified using flow cytometry.ResultsExpression of GPR15 was significantly increased on CD4+ effector T cells (CD4+ CD127+ CD45RO+) in NAFLD, ALD and PSC patients compared to healthy controls (9.7 ± 0.4, 12.7 ± 0.9 and 20.1 ± 1.8 vs 4.1 ± 1.8, P |
| doi_str_mv | 10.1136/gutjnl-2019-BSGAbstracts.219 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_bmj_p</sourceid><recordid>TN_cdi_proquest_journals_2241249520</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2241249520</sourcerecordid><originalsourceid>FETCH-LOGICAL-b1309-2b4093204a18b5a8cb801a78826be33d366d6455acd91c5084de4a8cca5dcc0a3</originalsourceid><addsrcrecordid>eNpNkMtKAzEUhoMoWKvvENDt1JPbTLKsRatQsNR2HTIzaTvDXGqSEdy58UV9ElPqwtU5cL7z__AhdEdgQghL73dDqLsmoUBU8vA2n-Y-OFMEP6FEnaER4alMGJXyHI0ASJaIjKtLdOV9DQBSKjJCdrneJEDg5-t71TcWb3uH58sVEdiZsLcOh73pcG6DwRmuumB3rup83OLB4kNk-p3trK887rfYDKGv2nboLG6qj_hdVt4ab6_RxdY03t78zTHaPD2uZ8_J4nX-MpsukpwwUAnNOShGgRsic2FkkUsgJpOSprllrGRpWqZcCFOUihQCJC8tj1hhRFkUYNgY3Z5yD65_H6wPuu4H18VKTSknlCtBIVLZicrbWh9c1Rr3qQnoo1N9cqqPTvV_pzo6Zb-x82_5</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2241249520</pqid></control><display><type>article</type><title>PTU-010 Role for GPR15 rather than beta 7 integrins in the pathogenesis of autoimmune liver disease</title><source>PubMed Central</source><creator>Graham, Jonathon ; Mukherjee, Suj ; Yuksel, Muhammed ; Liberal, Rodrigo ; Mieli-Vergani, Giorgina ; Vergani, Diego ; Ma, Yun ; Hayee, Bu</creator><creatorcontrib>Graham, Jonathon ; Mukherjee, Suj ; Yuksel, Muhammed ; Liberal, Rodrigo ; Mieli-Vergani, Giorgina ; Vergani, Diego ; Ma, Yun ; Hayee, Bu</creatorcontrib><description>IntroductionG protein-coupled receptor 15 (GPR15) is a chemoattractant receptor that directs homing of lymphocytes to the colon. Furthermore, it has been shown to be a mediator of effector T cell homing during intestinal inflammation. Evidence exists showing infiltration of gut derived α4β7+ and CCR9+ T cells in the hepatic infiltrate of patients with autoimmune liver disease (AILD), in particular primary sclerosing cholangitis (PSC), with expression of their complementary ligands also being identified on the hepatic endothelium. However, the role of GPR15 in hepatic gut T cell homing remains to be defined.MethodsExplanted liver tissue was collected from patients undergoing orthotopic liver transplantation for chronic liver disease (Alcoholic liver disease [ALD] n=3, Non-alcoholic fatty liver disease [NAFLD] n=3, PSC n=4) with healthy control tissue sourced from patients undergoing hepatocellular carcinoma (HCC) resection (n=4). Liver infiltrating lymphocytes (LIL) were isolated using a mechanical homogenisation and centrifugation/filtration technique. Expression of gut homing markers on T cells was quantified using flow cytometry.ResultsExpression of GPR15 was significantly increased on CD4+ effector T cells (CD4+ CD127+ CD45RO+) in NAFLD, ALD and PSC patients compared to healthy controls (9.7 ± 0.4, 12.7 ± 0.9 and 20.1 ± 1.8 vs 4.1 ± 1.8, P<0.05), with a significant increase also observed on CD8+ effector T cells (CD8+ CD45RO+) in PSC patients when compared to healthy controls (16.7 ± 2.6 vs 2.3 ± 0.58, P<0.01). There were also trends towards increased expression of gut homing markers CCR9, α4β7 and αEβ7 on effector CD4+ and CD8+ T cells in all chronic liver disease groups compared with healthy control tissue.Abstract PTU-010 Figure 1ConclusionsFor some time, evidence pointed towards β7 integrins as the drivers of the hepatic inflammation seen in patients with AILD and associated inflammatory bowel disease as a result of aberrant effector T cells homing from the gut to the liver. These data reveal a somewhat redundant role for β7 integrins, which could be regarded as a non-disease specific feature of advanced disease, and highlight GPR15 as the primary mediator of effector gut T cell homing.</description><identifier>ISSN: 0017-5749</identifier><identifier>EISSN: 1468-3288</identifier><identifier>DOI: 10.1136/gutjnl-2019-BSGAbstracts.219</identifier><language>eng</language><publisher>London: BMJ Publishing Group LTD</publisher><subject>CCR9 protein ; CD4 antigen ; CD8 antigen ; Centrifugation ; Cholangitis ; Colon ; Digestive system ; Effector cells ; Endothelium ; Fatty liver ; Flow cytometry ; Gastrointestinal tract ; Hepatocellular carcinoma ; Inflammatory bowel diseases ; Integrins ; Intestine ; Liver diseases ; Liver transplantation ; Lymphocytes ; Lymphocytes T</subject><ispartof>Gut, 2019-06, Vol.68 (Suppl 2), p.A116</ispartof><rights>2019, Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions</rights><rights>2019 2019, Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids></links><search><creatorcontrib>Graham, Jonathon</creatorcontrib><creatorcontrib>Mukherjee, Suj</creatorcontrib><creatorcontrib>Yuksel, Muhammed</creatorcontrib><creatorcontrib>Liberal, Rodrigo</creatorcontrib><creatorcontrib>Mieli-Vergani, Giorgina</creatorcontrib><creatorcontrib>Vergani, Diego</creatorcontrib><creatorcontrib>Ma, Yun</creatorcontrib><creatorcontrib>Hayee, Bu</creatorcontrib><title>PTU-010 Role for GPR15 rather than beta 7 integrins in the pathogenesis of autoimmune liver disease</title><title>Gut</title><description>IntroductionG protein-coupled receptor 15 (GPR15) is a chemoattractant receptor that directs homing of lymphocytes to the colon. Furthermore, it has been shown to be a mediator of effector T cell homing during intestinal inflammation. Evidence exists showing infiltration of gut derived α4β7+ and CCR9+ T cells in the hepatic infiltrate of patients with autoimmune liver disease (AILD), in particular primary sclerosing cholangitis (PSC), with expression of their complementary ligands also being identified on the hepatic endothelium. However, the role of GPR15 in hepatic gut T cell homing remains to be defined.MethodsExplanted liver tissue was collected from patients undergoing orthotopic liver transplantation for chronic liver disease (Alcoholic liver disease [ALD] n=3, Non-alcoholic fatty liver disease [NAFLD] n=3, PSC n=4) with healthy control tissue sourced from patients undergoing hepatocellular carcinoma (HCC) resection (n=4). Liver infiltrating lymphocytes (LIL) were isolated using a mechanical homogenisation and centrifugation/filtration technique. Expression of gut homing markers on T cells was quantified using flow cytometry.ResultsExpression of GPR15 was significantly increased on CD4+ effector T cells (CD4+ CD127+ CD45RO+) in NAFLD, ALD and PSC patients compared to healthy controls (9.7 ± 0.4, 12.7 ± 0.9 and 20.1 ± 1.8 vs 4.1 ± 1.8, P<0.05), with a significant increase also observed on CD8+ effector T cells (CD8+ CD45RO+) in PSC patients when compared to healthy controls (16.7 ± 2.6 vs 2.3 ± 0.58, P<0.01). There were also trends towards increased expression of gut homing markers CCR9, α4β7 and αEβ7 on effector CD4+ and CD8+ T cells in all chronic liver disease groups compared with healthy control tissue.Abstract PTU-010 Figure 1ConclusionsFor some time, evidence pointed towards β7 integrins as the drivers of the hepatic inflammation seen in patients with AILD and associated inflammatory bowel disease as a result of aberrant effector T cells homing from the gut to the liver. These data reveal a somewhat redundant role for β7 integrins, which could be regarded as a non-disease specific feature of advanced disease, and highlight GPR15 as the primary mediator of effector gut T cell homing.</description><subject>CCR9 protein</subject><subject>CD4 antigen</subject><subject>CD8 antigen</subject><subject>Centrifugation</subject><subject>Cholangitis</subject><subject>Colon</subject><subject>Digestive system</subject><subject>Effector cells</subject><subject>Endothelium</subject><subject>Fatty liver</subject><subject>Flow cytometry</subject><subject>Gastrointestinal tract</subject><subject>Hepatocellular carcinoma</subject><subject>Inflammatory bowel diseases</subject><subject>Integrins</subject><subject>Intestine</subject><subject>Liver diseases</subject><subject>Liver transplantation</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><issn>0017-5749</issn><issn>1468-3288</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNpNkMtKAzEUhoMoWKvvENDt1JPbTLKsRatQsNR2HTIzaTvDXGqSEdy58UV9ElPqwtU5cL7z__AhdEdgQghL73dDqLsmoUBU8vA2n-Y-OFMEP6FEnaER4alMGJXyHI0ASJaIjKtLdOV9DQBSKjJCdrneJEDg5-t71TcWb3uH58sVEdiZsLcOh73pcG6DwRmuumB3rup83OLB4kNk-p3trK887rfYDKGv2nboLG6qj_hdVt4ab6_RxdY03t78zTHaPD2uZ8_J4nX-MpsukpwwUAnNOShGgRsic2FkkUsgJpOSprllrGRpWqZcCFOUihQCJC8tj1hhRFkUYNgY3Z5yD65_H6wPuu4H18VKTSknlCtBIVLZicrbWh9c1Rr3qQnoo1N9cqqPTvV_pzo6Zb-x82_5</recordid><startdate>201906</startdate><enddate>201906</enddate><creator>Graham, Jonathon</creator><creator>Mukherjee, Suj</creator><creator>Yuksel, Muhammed</creator><creator>Liberal, Rodrigo</creator><creator>Mieli-Vergani, Giorgina</creator><creator>Vergani, Diego</creator><creator>Ma, Yun</creator><creator>Hayee, Bu</creator><general>BMJ Publishing Group LTD</general><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AF</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>BTHHO</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>M2P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope></search><sort><creationdate>201906</creationdate><title>PTU-010 Role for GPR15 rather than beta 7 integrins in the pathogenesis of autoimmune liver disease</title><author>Graham, Jonathon ; Mukherjee, Suj ; Yuksel, Muhammed ; Liberal, Rodrigo ; Mieli-Vergani, Giorgina ; Vergani, Diego ; Ma, Yun ; Hayee, Bu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b1309-2b4093204a18b5a8cb801a78826be33d366d6455acd91c5084de4a8cca5dcc0a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>CCR9 protein</topic><topic>CD4 antigen</topic><topic>CD8 antigen</topic><topic>Centrifugation</topic><topic>Cholangitis</topic><topic>Colon</topic><topic>Digestive system</topic><topic>Effector cells</topic><topic>Endothelium</topic><topic>Fatty liver</topic><topic>Flow cytometry</topic><topic>Gastrointestinal tract</topic><topic>Hepatocellular carcinoma</topic><topic>Inflammatory bowel diseases</topic><topic>Integrins</topic><topic>Intestine</topic><topic>Liver diseases</topic><topic>Liver transplantation</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Graham, Jonathon</creatorcontrib><creatorcontrib>Mukherjee, Suj</creatorcontrib><creatorcontrib>Yuksel, Muhammed</creatorcontrib><creatorcontrib>Liberal, Rodrigo</creatorcontrib><creatorcontrib>Mieli-Vergani, Giorgina</creatorcontrib><creatorcontrib>Vergani, Diego</creatorcontrib><creatorcontrib>Ma, Yun</creatorcontrib><creatorcontrib>Hayee, Bu</creatorcontrib><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>Science Database (Alumni Edition)</collection><collection>STEM Database</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</collection><collection>BMJ Journals</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>Science 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>ProQuest Central Basic</collection><jtitle>Gut</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Graham, Jonathon</au><au>Mukherjee, Suj</au><au>Yuksel, Muhammed</au><au>Liberal, Rodrigo</au><au>Mieli-Vergani, Giorgina</au><au>Vergani, Diego</au><au>Ma, Yun</au><au>Hayee, Bu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PTU-010 Role for GPR15 rather than beta 7 integrins in the pathogenesis of autoimmune liver disease</atitle><jtitle>Gut</jtitle><date>2019-06</date><risdate>2019</risdate><volume>68</volume><issue>Suppl 2</issue><spage>A116</spage><pages>A116-</pages><issn>0017-5749</issn><eissn>1468-3288</eissn><abstract>IntroductionG protein-coupled receptor 15 (GPR15) is a chemoattractant receptor that directs homing of lymphocytes to the colon. Furthermore, it has been shown to be a mediator of effector T cell homing during intestinal inflammation. Evidence exists showing infiltration of gut derived α4β7+ and CCR9+ T cells in the hepatic infiltrate of patients with autoimmune liver disease (AILD), in particular primary sclerosing cholangitis (PSC), with expression of their complementary ligands also being identified on the hepatic endothelium. However, the role of GPR15 in hepatic gut T cell homing remains to be defined.MethodsExplanted liver tissue was collected from patients undergoing orthotopic liver transplantation for chronic liver disease (Alcoholic liver disease [ALD] n=3, Non-alcoholic fatty liver disease [NAFLD] n=3, PSC n=4) with healthy control tissue sourced from patients undergoing hepatocellular carcinoma (HCC) resection (n=4). Liver infiltrating lymphocytes (LIL) were isolated using a mechanical homogenisation and centrifugation/filtration technique. Expression of gut homing markers on T cells was quantified using flow cytometry.ResultsExpression of GPR15 was significantly increased on CD4+ effector T cells (CD4+ CD127+ CD45RO+) in NAFLD, ALD and PSC patients compared to healthy controls (9.7 ± 0.4, 12.7 ± 0.9 and 20.1 ± 1.8 vs 4.1 ± 1.8, P<0.05), with a significant increase also observed on CD8+ effector T cells (CD8+ CD45RO+) in PSC patients when compared to healthy controls (16.7 ± 2.6 vs 2.3 ± 0.58, P<0.01). There were also trends towards increased expression of gut homing markers CCR9, α4β7 and αEβ7 on effector CD4+ and CD8+ T cells in all chronic liver disease groups compared with healthy control tissue.Abstract PTU-010 Figure 1ConclusionsFor some time, evidence pointed towards β7 integrins as the drivers of the hepatic inflammation seen in patients with AILD and associated inflammatory bowel disease as a result of aberrant effector T cells homing from the gut to the liver. These data reveal a somewhat redundant role for β7 integrins, which could be regarded as a non-disease specific feature of advanced disease, and highlight GPR15 as the primary mediator of effector gut T cell homing.</abstract><cop>London</cop><pub>BMJ Publishing Group LTD</pub><doi>10.1136/gutjnl-2019-BSGAbstracts.219</doi><oa>free_for_read</oa></addata></record> |
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| subjects | CCR9 protein CD4 antigen CD8 antigen Centrifugation Cholangitis Colon Digestive system Effector cells Endothelium Fatty liver Flow cytometry Gastrointestinal tract Hepatocellular carcinoma Inflammatory bowel diseases Integrins Intestine Liver diseases Liver transplantation Lymphocytes Lymphocytes T |
| title | PTU-010 Role for GPR15 rather than beta 7 integrins in the pathogenesis of autoimmune liver disease |
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