{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T18:13:08Z","timestamp":1778004788311,"version":"3.51.4"},"reference-count":35,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Shandong Natural Science Foundation","doi-asserted-by":"crossref","award":["ZR2022MH141 and ZR2016HM19"],"award-info":[{"award-number":["ZR2022MH141 and ZR2016HM19"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Clinical X+ project of Binzhou Medical University","award":["BY2021LCX12"],"award-info":[{"award-number":["BY2021LCX12"]}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>\n                    <jats:italic>Clonorchis sinensis<\/jats:italic>\n                    (\n                    <jats:italic>C. sinensis<\/jats:italic>\n                    ) infection causes serious pathological changes of hepatobiliary system such as hyperplasia of the biliary mucosa, inflammation and periductal fibrosis. The excretory-secretory products of\n                    <jats:italic>C. sinensis<\/jats:italic>\n                    (CsESPs) play critical roles in triggering inflammation and subsequent activation of hepatic stellate cells (HSCs). Yet, how CsESPs induce hepatic fibrosis through breaking the barrier of biliary epithelium remains unclear. Previous studies have confirmed that interleukin-17A (IL-17A) promoted fibrosis in some liver diseases. In the present study, the IL-17A levels in the serum of\n                    <jats:italic>C. sinensis<\/jats:italic>\n                    infected patients and healthy people were compared.\n                    <jats:italic>C. sinensis<\/jats:italic>\n                    infected mouse model was applied to discover the expression of IL-17A, especially its localization in the biliary epithelium. Cells and bile duct organoid models were established to evaluate the effect of CsESPs on the production of IL-17A by biliary epithelium and subsequent activation of HSCs. The results indicated that the levels of IL-17A were higher in the serum of patients and mice infected with\n                    <jats:italic>C. sinensis<\/jats:italic>\n                    than in the healthy people and control mice respectively. Infected mouse liver showed increased collagen deposition and marked hyperplasia of the intrahepatic bile duct with significant expression of IL-17A. CsESPs-stimulated human cholangiocarcinoma cells (RBE) displayed elevated proliferation ability and produced higher level of IL-17A. Supernatant of CsESPs-RBE cells activated human hepatic stellate cells (LX-2) with upregulated production of \u03b1-SMA and collagen I. Knocking down of\n                    <jats:italic>IL-17A<\/jats:italic>\n                    in RBE cells by lentivirus attenuated the expression of \u03b1-SMA and collagen I in LX-2 cells incubated with supernatants of CsESPs-stimulated RBE cells. Under stimulation of CsESPs, the bile duct organoids became swelled with thickened and deformable walls and prominent IL-17A signals. These findings suggest that CsESPs may activate HSCs through a new pathway of stimulating biliary epithelium to produce IL-17A.\n                  <\/jats:p>","DOI":"10.1371\/journal.pntd.0014280","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T17:35:25Z","timestamp":1778002525000},"page":"e0014280","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clonorchis sinensis excretory secretory products promote hepatic fibrosis through stimulating biliary epithelium to secrete 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