{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T11:31:41Z","timestamp":1771327901294,"version":"3.50.1"},"reference-count":40,"publisher":"Portland Press Ltd.","issue":"7","license":[{"start":{"date-parts":[[2021,3,26]],"date-time":"2021-03-26T00:00:00Z","timestamp":1616716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,4,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Biliary atresia (BA) is an immune-related disorder and signal transducer and activator of transcription 3 (STAT3) is a key signalling molecule in inflammation. The present study was designed to clarify the function of STAT3 in BA. STAT3 expression was examined in patients and a mouse BA model in which STAT3 levels were further altered with a specific inhibitor or activator. Neutrophil accumulation and the levels of the neutrophil chemoattractants (C\u2013X\u2013C motif) ligand 1 (CXCL1) and IL-8 were determined. The effects of STAT3 inhibition on IL-8 expression were examined in human biliary epithelial cell (BEC) cultures. Functional changes in liver STAT3+ neutrophils in the mouse model were analysed with 10\u00d7 single cell RNA-seq methods. Results showed STAT3 and p-STAT3 expression was reduced in BA liver tissue compared with control samples. Administration of a STAT3 inhibitor increased jaundice and mortality and reduced body weight in BA mice. In contrast, the STAT3 activator ameliorated BA symptoms. Extensive neutrophil accumulation together with CXCL1 up-regulation, both of which were suppressed by an anti-CXCL1 antibody, were observed in the STAT3 inhibitor-treated group. Recombinant IL-8 administration increased disease severity in BA mice, and the STAT3 activator had the reverse effect. Inhibiting STAT3 increased apoptosis of human BECs together with up-regulated IL-8 expression. RNA-seq analysis revealed reduced the numbers of STAT3 expressing neutrophil in BA which was accompanied by marked enhanced interferon-related antiviral activities. In conclusion, STAT3 reduction, enhanced IL-8 and CXCL1 expression and promoted the accumulation of interferon-responsive neutrophils resulting in BEC damage in BA.<\/jats:p>","DOI":"10.1042\/cs20201366","type":"journal-article","created":{"date-parts":[[2021,3,26]],"date-time":"2021-03-26T10:19:10Z","timestamp":1616753950000},"page":"865-884","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Down-regulation of STAT3 enhanced chemokine expression and neutrophil recruitment in biliary atresia"],"prefix":"10.1042","volume":"135","author":[{"given":"Ming","family":"Fu","sequence":"first","affiliation":[{"name":"Provincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangzhou Women and Children\u2019s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China"},{"name":"First Affiliated Hospital of Jinan University, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ledong","family":"Tan","sequence":"additional","affiliation":[{"name":"Provincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangzhou Women and Children\u2019s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zefeng","family":"Lin","sequence":"additional","affiliation":[{"name":"Provincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangzhou Women and Children\u2019s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent\u00a0C.H.","family":"Lui","sequence":"additional","affiliation":[{"name":"Department of Surgery, The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul\u00a0K.H.","family":"Tam","sequence":"additional","affiliation":[{"name":"Department of Surgery, The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5497-392X","authenticated-orcid":false,"given":"Jonathan\u00a0R.","family":"Lamb","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, London, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9556-0240","authenticated-orcid":false,"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Provincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangzhou Women and Children\u2019s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0103-1672","authenticated-orcid":false,"given":"Huimin","family":"Xia","sequence":"additional","affiliation":[{"name":"Provincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangzhou Women and Children\u2019s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruizhong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Provincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangzhou Women and Children\u2019s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2354-230X","authenticated-orcid":false,"given":"Yan","family":"Chen","sequence":"additional","affiliation":[{"name":"Provincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangzhou Women and Children\u2019s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China"},{"name":"Department of Surgery, The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2021,4,9]]},"reference":[{"key":"2021113011203046100_B1","doi-asserted-by":"publisher","first-page":"1704","DOI":"10.1016\/S0140-6736(09)60946-6","article-title":"Biliary atresia","volume":"374","author":"Hartley","year":"2009","journal-title":"Lancet"},{"key":"2021113011203046100_B2","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1097\/MOG.0000000000000509","article-title":"Genetics in biliary atresia","volume":"35","author":"Girard","year":"2019","journal-title":"Curr. 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Nutr."},{"key":"2021113011203046100_B5","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1542\/peds.2004-1900","article-title":"Promoter polymorphism of the CD14 endotoxin receptor gene is associated with biliary atresia and idiopathic neonatal cholestasis","volume":"116","author":"Shih","year":"2005","journal-title":"Pediatrics"},{"key":"2021113011203046100_B6","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1159\/000352025","article-title":"Polymorphism of ITGB2 gene 3\u2032-UTR+145C\/A is associated with biliary atresia","volume":"88","author":"Zhao","year":"2013","journal-title":"Digestion"},{"key":"2021113011203046100_B7","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1159\/000371694","article-title":"Genetic contributors and modifiers of biliary atresia","volume":"33","author":"Mezina","year":"2015","journal-title":"Dig. 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