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Here, we report increased accumulation of \u03b14\u03b27+ T cells in the liver of people with cirrhosis relative to disease controls. Similarly, hepatic fibrosis in the established mouse model of CCl4-induced liver fibrosis was associated with enrichment of intrahepatic \u03b14\u03b27+ CD4 and CD8 T cells. Monoclonal antibody (mAb)-mediated blockade of \u03b14\u03b27 or its ligand mucosal addressin cell adhesion molecule (MAdCAM)-1 attenuated hepatic inflammation and prevented fibrosis progression in CCl4-treated mice. Improvement in liver fibrosis was associated with a significant decrease in the infiltration of \u03b14\u03b27+ CD4 and CD8 T cells, suggesting that \u03b14\u03b27\/MAdCAM-1 axis regulates both CD4 and CD8 T cell recruitment to the fibrotic liver, and \u03b14\u03b27+ T cells promote hepatic fibrosis progression. Analysis of hepatic \u03b14\u03b27+ and \u03b14\u03b27- CD4 T cells revealed that \u03b14\u03b27+ CD4 T cells were enriched for markers of activation and proliferation, demonstrating an effector phenotype. The findings suggest that \u03b14\u03b27+ T cells play a critical role in promoting hepatic fibrosis progression, and mAb-mediated blockade of \u03b14\u03b27 or MAdCAM-1 represents a promising therapeutic strategy for slowing hepatic fibrosis progression in chronic liver diseases.<\/jats:p>","DOI":"10.3390\/cells13090756","type":"journal-article","created":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T08:42:57Z","timestamp":1714639377000},"page":"756","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Selective Targeting of \u03b14\u03b27\/MAdCAM-1 Axis Suppresses Fibrosis Progression by Reducing Proinflammatory T Cell Recruitment to the Liver"],"prefix":"10.3390","volume":"13","author":[{"given":"Biki","family":"Gupta","sequence":"first","affiliation":[{"name":"Division of Experimental Pathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2550-3811","authenticated-orcid":false,"given":"Ravi Prakash","family":"Rai","sequence":"additional","affiliation":[{"name":"Division of Experimental Pathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pabitra B.","family":"Pal","sequence":"additional","affiliation":[{"name":"Division of Experimental Pathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Rossmiller","sequence":"additional","affiliation":[{"name":"Division of Experimental Pathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, 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University of Pittsburgh, Pittsburgh, PA 15261, USA"},{"name":"Division of Anatomic Pathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1840-9520","authenticated-orcid":false,"given":"Silvia","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Experimental Pathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA"},{"name":"Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA 15261, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8437-3378","authenticated-orcid":false,"given":"Satdarshan P.","family":"Monga","sequence":"additional","affiliation":[{"name":"Division of Experimental Pathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, 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