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Here, we explored the role of PVR in BA pathogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Poliovirus receptor expression and NK cell\u2010associated genes were detected in human BA samples and a rotavirus\u2010induced BA mouse model using quantitative PCR and immunofluorescence staining. Chemically modified small interfering RNA silenced PVR expression in the BA model, and its effects on the population and function of intrahepatic NK cells were investigated using flow cytometry (FCM). The effects of PVR overexpression and knockdown on proliferation, apoptosis and NK\u2010cell\u2010mediated lysis of cultured human cholangiocytes were analysed using FCM and cell viability assays. Serum PVR, high\u2010mobility group box 1 (HMGB1), and interleukin\u20101beta (IL\u20101beta) levels were measured in a cohort of 50 patients using ELISA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Poliovirus receptor expression was upregulated in the biliary epithelium of BA patients and BA model and was positively correlated with the population and activation of intrahepatic NK cells. Silencing of PVR expression impaired the cytotoxicity of NK cells, reduced inflammation and protected mice from rotavirus\u2010induced BA. Activation of the TLR3\u2010IRF3 signalling pathway induced PVR expression in cultured cholangiocytes. PVR overexpression promoted proliferation and inhibited the apoptosis of cholangiocytes but exacerbated NK cell\u2010mediated cholangiocyte lysis. Serum PVR levels were elevated in BA patients and were positively correlated with HMGB1 and IL\u20101beta levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Poliovirus receptor contributes to BA pathogenesis by regulating NK cell\u2010mediated bile duct injury; PVR has the value as a biomarker of BA.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.15457","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T16:59:21Z","timestamp":1666025961000},"page":"2724-2742","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Human poliovirus receptor contributes to biliary atresia pathogenesis by exacerbating natural\u2010killer\u2010cell\u2010mediated bile duct injury"],"prefix":"10.1111","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8398-7482","authenticated-orcid":false,"given":"Yuan","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pediatric Surgery Shengjing Hospital of China Medical University  Shenyang People's Republic of China"},{"name":"The Key Laboratory of Health Ministry for Congenital Malformation Shengjing Hospital of China Medical University  Shenyang People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian\u2010Yu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery Shengjing Hospital of China Medical University  Shenyang People's Republic of China"},{"name":"The Key Laboratory of Health Ministry for Congenital Malformation Shengjing Hospital of China Medical University  Shenyang People's Republic of 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