{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T20:43:05Z","timestamp":1764103385637,"version":"3.43.0"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,2,20]],"date-time":"2023-02-20T00:00:00Z","timestamp":1676851200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Basic Research Program of China","doi-asserted-by":"publisher","award":["2016YFA0101003"],"award-info":[{"award-number":["2016YFA0101003"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81571594","81771764"],"award-info":[{"award-number":["81571594","81771764"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Rheum Dis"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>To verify the role of CX3C chemokine ligand 1 \u2010 CX3C chemokine receptor 1 (CX3CL1\u2010CX3CR1) pathway in the pathogenesis of primary biliary cholangitis (PBC). To explore whether CCL26, a novel functional ligand to CX3CR1, participates in the immunological mechanism of PBC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Fifty\u2010nine PBC patients and 54 healthy controls were recruited. Enzyme\u2010linked immunosorbent assay and flow cytometry were used to measure CX3CL1 and CCL26 concentrations in plasma and CX3CR1 expression on peripheral lymphocytes, respectively. Chemotactic effects of CX3CL1 and CCL26 toward lymphocytes were detected by Transwell cell migration assays. CX3CL1 and CCL26 expressions in liver were assessed by immunohistochemical staining. Effects of CX3CL1 and CCL26 on stimulating cytokine production from lymphocytes were evaluated using intracellular flow cytometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Significantly elevated CX3CL1 and CCL26 plasma concentration and CX3CR1 expression on CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cells were noted in PBC patients. CX3CL1 exhibited chemotactic activity toward CD8<jats:sup>+<\/jats:sup> T, natural killer (NK) and NKT cells in a dose\u2010dependent manner while such chemotactic effects were not detected for CCL26. In PBC patients, CX3CL1 and CCL26 were both increasingly expressed in biliary tracts and a concentration gradient of CCL26 in hepatocytes around portal areas was observed. Immobilized CX3CL1 could enhance interferon\u2010\u03b3 production from T and NK cells while such effect was not exhibited by soluble CX3CL1 or CCL26.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>CCL26 expression is significantly elevated in plasma and biliary duct of PBC patients, yet does not appear to attract CX3CR1\u2010expressing immune cells. CX3CL1\u2010CX3CR1 pathway promotes the infiltration of T, NK and NKT cells into bile ducts and forms a positive feedback loop with T\u2010helper 1 type cytokines in PBC.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1756-185x.14578","type":"journal-article","created":{"date-parts":[[2023,2,20]],"date-time":"2023-02-20T23:50:11Z","timestamp":1676937011000},"page":"648-656","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp>CCL26<\/scp> in primary biliary cholangitis \u2013 Is it a novel disease mediator?"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3697-6737","authenticated-orcid":false,"given":"Xiaochuan","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Rheumatology, Peking Union Medical College Hospital Peking Union Medical College and Chinese Academy of Medical Science  Beijing 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