{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:46:05Z","timestamp":1786977965189,"version":"build-2736575974"},"reference-count":52,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2020,10,1]],"date-time":"2020-10-01T00:00:00Z","timestamp":1601510400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>T cells from patients with primary sclerosing cholangitis (PSC) show a prominent interleukin (IL)\u201017 response upon stimulation with bacteria or fungi, yet the reasons for this dominant T\u2010helper 17 (Th17) response in PSC are not clear. Here, we analyzed the potential role of monocytes in microbial recognition and in skewing the T\u2010cell response toward Th17.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach and Results<\/jats:title>\n                    <jats:p>\n                      Monocytes and T cells from blood and livers of PSC patients and controls were analyzed\n                      <jats:italic toggle=\"yes\">ex vivo<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      using transwell experiments with cholangiocytes. Cytokine production was measured using flow cytometry, enzyme\u2010linked immunosorbent assay, RNA\n                      <jats:italic toggle=\"yes\">in situ<\/jats:italic>\n                      hybridization, and quantitative real\u2010time PCR. Genetic polymorphisms were obtained from ImmunoChip analysis. Following e\n                      <jats:italic toggle=\"yes\">x vivo<\/jats:italic>\n                      stimulation with phorbol myristate acetate\/ionomycin, PSC patients showed significantly increased numbers of IL\u201017A\u2013producing peripheral blood CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells compared to PBC patients and healthy controls, indicating increased Th17 differentiation\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      . Upon stimulation with microbes, monocytes from PSC patients produced significantly more IL\u20101\u03b2 and IL\u20106, cytokines known to drive Th17 cell differentiation. Moreover, microbe\u2010activated monocytes induced the secretion of Th17 and monocyte\u2010recruiting chemokines chemokine (C\u2010C motif) ligand (CCL)\u201020 and CCL\u20102 in human primary cholangiocytes. In livers of patients with PSC cirrhosis, CD14\n                      <jats:sup>hi<\/jats:sup>\n                      CD16\n                      <jats:sup>int<\/jats:sup>\n                      and CD14\n                      <jats:sup>lo<\/jats:sup>\n                      CD16\n                      <jats:sup>hi<\/jats:sup>\n                      monocytes\/macrophages were increased compared to alcoholic cirrhosis, and monocytes were found to be located around bile ducts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      PSC patients show increased Th17 differentiation already\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      . Microbe\u2010stimulated monocytes drive Th17 differentiation\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      and induce cholangiocytes to produce chemokines mediating recruitment of Th17 cells and more monocytes into portal tracts. Taken together, these results point to a pathogenic role of monocytes in patients with PSC.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.31140","type":"journal-article","created":{"date-parts":[[2020,1,24]],"date-time":"2020-01-24T00:11:13Z","timestamp":1579824673000},"page":"1310-1326","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":92,"title":["Monocytes as Potential Mediators of Pathogen\u2010Induced T\u2010Helper 17 Differentiation in Patients With Primary Sclerosing Cholangitis (PSC)"],"prefix":"10.1097","volume":"72","author":[{"given":"Lilly Kristin","family":"Kunzmann","sequence":"first","affiliation":[{"name":"1st Department of Medicine,University Medical Center Hamburg\u2010Eppendorf,Hamburg,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Schoknecht","sequence":"additional","affiliation":[{"name":"1st Department of Medicine,University Medical Center Hamburg\u2010Eppendorf,Hamburg,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Poch","sequence":"additional","affiliation":[{"name":"1st Department of Medicine,University Medical Center Hamburg\u2010Eppendorf,Hamburg,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9585-7864","authenticated-orcid":false,"given":"Lara","family":"Henze","sequence":"additional","affiliation":[{"name":"1st Department of Medicine,University Medical Center Hamburg\u2010Eppendorf,Hamburg,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Stein","sequence":"additional","affiliation":[{"name":"1st Department of Medicine,University Medical Center Hamburg\u2010Eppendorf,Hamburg,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marvin","family":"Kriz","sequence":"additional","affiliation":[{"name":"1st Department of 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