{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:24:41Z","timestamp":1790677481118,"version":"4.1.0"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T00:00:00Z","timestamp":1638835200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T00:00:00Z","timestamp":1638835200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>The \u201cgut homing\u201d hypothesis suggests the pathogenesis of primary sclerosing cholangitis (PSC) is driven by aberrant hepatic expression of gut adhesion molecules and subsequent recruitment of gut\u2010derived T cells to the liver. However, inconsistencies lie within this theory including an absence of investigations and comparisons with other chronic liver diseases (CLD). Here, we examine \u201cthe gut homing theory\u201d in patients with PSC with associated inflammatory bowel disease (PSC\u2010IBD) and across multiple inflammatory liver diseases.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>Expression of MAdCAM\u20101, CCL25, and E\u2010Cadherin were assessed histologically and using RT\u2010PCR on explanted liver tissue from patients with CLD undergoing OLT and in normal liver. Liver mononuclear cells were isolated from explanted tissue samples and the expression of gut homing integrins and cytokines on hepatic infiltrating gut\u2010derived T cells was assessed using flow cytometry. Hepatic expression of MAdCAM\u20101, CCL25 and E\u2010Cadherin was up\u2010regulated in all CLDs compared with normal liver. There were no differences between disease groups. Frequencies of \u03b14\u03b27, \u03b1E\u03b27, CCR9, and GPR15 expressing hepatic T cells was increased in PSC\u2010IBD, but also in CLD controls, compared with normal liver. \u03b27 expressing hepatic T cells displayed an increased inflammatory phenotype compared with \u03b27 negative cells, although this inflammatory cytokine profile was present in both the inflamed and normal liver.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>These findings refute the widely accepted \u201cgut homing\u201d hypothesis as the primary driver of PSC and indicate that aberrant hepatic recruitment of gut\u2010derived T cells is not unique to PSC, but is a panetiological feature of CLD.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.32193","type":"journal-article","created":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T07:57:36Z","timestamp":1634111856000},"page":"518-530","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":49,"title":["Aberrant hepatic trafficking of gut\u2010derived T cells is not specific to primary sclerosing cholangitis"],"prefix":"10.1097","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1637-7024","authenticated-orcid":false,"given":"Jonathon J.","family":"Graham","sequence":"first","affiliation":[{"name":"Institute of Liver Studies,School of Immunology & Microbial Sciences,Faculty of Life Sciences & Medicine,King\u2019s College London,King\u2019s College Hospital,London,UK"},{"name":"Department of Anesthesia,Critical Care & Pain Medicine,Beth Israel Deaconess Medical Center,Harvard Medical School,Boston,Massachusetts,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujit","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"Section of Hepatology,Department of Metabolism Digestion and Reproduction,Faculty of Medicine,Imperial College London,London,UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Yuksel","sequence":"additional","affiliation":[{"name":"Institute of Liver Studies,School of Immunology & Microbial Sciences,Faculty of Life Sciences & Medicine,King\u2019s College London,King\u2019s College Hospital,London,UK"},{"name":"Ko\u00e7 University Research Centre for Translational Medicine,Istanbul,Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebeca","family":"Sanabria Mateos","sequence":"additional","affiliation":[{"name":"Institute of Liver Studies,School of Immunology & Microbial Sciences,Faculty of Life Sciences & Medicine,King\u2019s College London,King\u2019s College Hospital,London,UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tengfei","family":"Si","sequence":"additional","affiliation":[{"name":"Institute of Liver Studies,School of Immunology & Microbial Sciences,Faculty of Life Sciences & Medicine,King\u2019s College London,King\u2019s College Hospital,London,UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenlin","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Liver Studies,School of Immunology & Microbial Sciences,Faculty of Life Sciences & Medicine,King\u2019s College London,King\u2019s College Hospital,London,UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiahong","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Liver Studies,School of Immunology & Microbial Sciences,Faculty of Life Sciences & Medicine,King\u2019s College London,King\u2019s College Hospital,London,UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadil","family":"Abu Arqoub","sequence":"additional","affiliation":[{"name":"Liver Histopathology Laboratory,Institute of Liver Studies,King\u2019s College London,London,UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6616-3628","authenticated-orcid":false,"given":"Vishal","family":"Patel","sequence":"additional","affiliation":[{"name":"Institute of Liver Studies,School of Immunology & Microbial Sciences,Faculty of Life Sciences & Medicine,King\u2019s College London,King\u2019s College Hospital,London,UK"},{"name":"The Roger Williams Institute of Hepatology London,Foundation for Liver Research,London,UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"McPhail","sequence":"additional","affiliation":[{"name":"Institute of Liver Studies,School of Immunology & Microbial Sciences,Faculty of Life Sciences & Medicine,King\u2019s College London,King\u2019s College Hospital,London,UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoh","family":"Zen","sequence":"additional","affiliation":[{"name":"Liver Histopathology Laboratory,Institute of Liver Studies,King\u2019s College London,London,UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigel","family":"Heaton","sequence":"additional","affiliation":[{"name":"Institute of Liver Studies,School of Immunology & Microbial Sciences,Faculty of Life Sciences & Medicine,King\u2019s College London,King\u2019s College Hospital,London,UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Serena","family":"Longhi","sequence":"additional","affiliation":[{"name":"Department of Anesthesia,Critical Care & Pain Medicine,Beth Israel Deaconess Medical Center,Harvard Medical School,Boston,Massachusetts,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Heneghan","sequence":"additional","affiliation":[{"name":"Institute of Liver Studies,School of Immunology & Microbial Sciences,Faculty of Life Sciences & Medicine,King\u2019s College London,King\u2019s College Hospital,London,UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Liberal","sequence":"additional","affiliation":[{"name":"Institute of Liver Studies,School of Immunology & Microbial Sciences,Faculty of Life Sciences & Medicine,King\u2019s College London,King\u2019s College Hospital,London,UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Vergani","sequence":"additional","affiliation":[{"name":"Institute of Liver Studies,School of Immunology & Microbial Sciences,Faculty of Life Sciences & Medicine,King\u2019s College London,King\u2019s College Hospital,London,UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgina","family":"Mieli\u2010Vergani","sequence":"additional","affiliation":[{"name":"Paediatric Liver, GI and Nutrition Centre,Mowat Labs,King\u2019s College London Faculty of Life Sciences & Medicine at King's College Hospital,London,UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Ma","sequence":"additional","affiliation":[{"name":"Institute of Liver Studies,School of Immunology & Microbial Sciences,Faculty of Life Sciences & Medicine,King\u2019s College London,King\u2019s College Hospital,London,UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bu\u2019Hussain","family":"Hayee","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology,School of Immunology & Microbial Sciences,Faculty of Life Sciences & Medicine,King\u2019s College London,King\u2019s College 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