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The pathogenesis is unknown but a strong immune cell component has been suggested. Mucosal\u2010associated invariant T (MAIT) cells are abundant in human liver and localize around bile ducts. Yet, the role of MAIT cells in PSC remains unclear. Here, we performed a detailed characterization of MAIT cells in circulation and assessed their presence in bile ducts of PSC patients as well as non\u2010PSC controls. We observed a dramatic reduction in MAIT cell levels in PSC patients. High\u2010dimensional phenotypical analysis using stochastic neighbor embedding revealed the MAIT cells to be activated, a phenotype shared by the investigated disease control groups. In line with the noted phenotypic alterations, MAIT cell function was reduced in response to <jats:italic>Escherichia coli<\/jats:italic> and to cytokine stimulation in PSC patients as compared to healthy controls. Using a novel sampling approach of human bile ducts, we found MAIT cells to be specifically enriched within bile ducts. Finally, distinct from the dramatic decline observed in circulation, PSC\u2010patients had retained levels of MAIT cells within bile ducts. Altogether, our results provide a detailed insight into how the human MAIT cell compartment is affected in PSC.<\/jats:p>","DOI":"10.1002\/eji.201847608","type":"journal-article","created":{"date-parts":[[2018,9,25]],"date-time":"2018-09-25T16:27:14Z","timestamp":1537892834000},"page":"1997-2004","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Primary sclerosing cholangitis leads to dysfunction and loss of MAIT cells"],"prefix":"10.1002","volume":"48","author":[{"given":"Erik","family":"von Seth","sequence":"first","affiliation":[{"name":"Division of Hepatology Department of Upper GI Diseases Karolinska University Hospital  Stockholm Sweden"},{"name":"Unit of Gastroenterology and Rheumatology Department of Medicine Huddinge Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine L.","family":"Zimmer","sequence":"additional","affiliation":[{"name":"Center 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