{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T14:59:13Z","timestamp":1792162753011,"version":"4.4.0"},"reference-count":34,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Hepatic steatosis is characterised by hepatic lipid accumulation, inflammation and fibrosis, with macrophage polarisation playing a central role in disease progression. This study investigates the role of interleukin\u201025 (IL\u201025) in modulating macrophage polarisation and Notch signalling in a methionine\u2010choline\u2010deficient (MCD) diet\u2010induced metabolic dysfunction\u2010associated fatty liver disease (MAFLD) model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>C57BL\/6 mice were fed a MCD diet to induce MAFLD. Human hepatocytes and primary hepatic macrophages were treated with palmitic acid and\/or IL\u201025. Methods included RT\u2010qPCR, ELISA, Western blot and immunofluorescence for gene\/protein expression. ChIP and luciferase assays were used to analyse STAT3\/Notch\u20101 signalling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found that IL\u201025 expression was significantly downregulated in the livers of MCD\u2010fed mice and in palmitic acid\u2010treated hepatocytes. IL\u201025 treatment promoted M2 macrophage polarisation, evidenced by increased expression of Arg1, Chi3l3 and anti\u2010inflammatory cytokines (IL\u201010, TGF\u2010\u03b2), while suppressing pro\u2010inflammatory cytokines (TNF\u2010\u03b1, IL\u20106). Mechanistically, IL\u201025 inhibited the STAT3\/Notch\u20101 pathway and induced IL\u201033, which negatively regulated the NF\u2010\u03baB\/Jagged\u20101 axis, preventing M1 macrophage polarisation. Adoptive transfer of IL\u201025\u2010induced M2a macrophages ameliorated hepatic steatosis and reduced ductular reaction in MCD\u2010fed mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings suggest a role for IL\u201025 in modulating macrophage polarisation and inflammation in metabolic dysfunction\u2010associated fatty liver disease, supporting its further exploration as a potential therapeutic strategy for inflammatory liver diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70370","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T17:44:03Z","timestamp":1759513443000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["<scp>IL<\/scp>\n                    \u201025 Improves\n                    <scp>MAFLD<\/scp>\n                    by Suppressing the Notch Signalling in Hepatic Macrophages"],"prefix":"10.1111","volume":"45","author":[{"given":"Xuelian","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Shenzhen Clinical Research Center for Digestive Disease Shenzhen Hospital, Southern Medical University  Shenzhen China"},{"name":"Department of Pharmacy Shenzhen Hospital, Southern Medical University  Shenzhen China"},{"name":"Department of Pharmacy The First Affiliated Hospital of Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Hu","sequence":"additional","affiliation":[{"name":"Guangzhou Women and Children's Medical Center Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongjing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Shenzhen Clinical Research Center for Digestive Disease Shenzhen Hospital, Southern Medical University  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Shenzhen Clinical Research Center for Digestive Disease Shenzhen Hospital, Southern Medical University  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianrui","family":"Wei","sequence":"additional","affiliation":[{"name":"Guangzhou Women and Children's Medical Center Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Xie","sequence":"additional","affiliation":[{"name":"Faculty of Forensic Medicine, Zhongshan School of Medicine, and Guangdong Province Translational Forensic Medicine Engineering Technology Research Center Sun Yat\u2010sen University  Guangzhou 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