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Methods: HBV transgenic (HBs-Tg) mice were used to investigate intrahepatic NK cells in two distinct subsets: conventional NK (cNK) and liver-resident NK (LrNK) cells during a chronic HBV infection. Results: The cNK cells, but not the LrNK cells, were primarily responsible for the increase in the number of bulk NK cells in the livers of ageing HBs-Tg mice. The hepatic cNK cells showed a stronger ability to produce IL-10, coupled with a higher expression of CD69, TIGIT and PD-L1, and lower NKG2D expression in ageing HBs-Tg mice. A lower mitochondrial mass and membrane potential, and less polarized localization were observed in the hepatic cNK cells compared with the splenic cNK cells in the HBs-Tg mice. The enhanced galectin-3 (Gal-3) secreted from HBsAg+ hepatocytes accounted for the IL-10 production of hepatic cNK cells via ITGB1 signaling. For humans, LGALS3 and ITGB1 expression is positively correlated with IL-10 expression, and negatively correlated with the poor clinical progression of HCC. Conclusions: Gal-3-ITGB1 signaling shapes hepatic cNK cells but not LrNK cells during a chronic HBV infection, which may correlate with HCC progression.<\/jats:p>","DOI":"10.3390\/v16050737","type":"journal-article","created":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T06:53:27Z","timestamp":1715064807000},"page":"737","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Galectin-3-ITGB1 Signaling Mediates Interleukin 10 Production of Hepatic Conventional Natural Killer Cells in Hepatitis B Virus Transgenic Mice and Correlates with Hepatocellular Carcinoma Progression in Patients"],"prefix":"10.3390","volume":"16","author":[{"given":"Yongyan","family":"Chen","sequence":"first","affiliation":[{"name":"Key Laboratory of Immune Response and Immunotherapy, Institute of Immunology, Biomedical Sciences and Health Laboratory of Anhui Province, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China"},{"name":"Research Unit of NK Cell Study, Chinese Academy of Medical Sciences, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Immune Response and Immunotherapy, Institute of Immunology, Biomedical Sciences and Health Laboratory of Anhui Province, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Cheng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Immune Response and Immunotherapy, Institute of Immunology, Biomedical Sciences and Health Laboratory of Anhui Province, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China"},{"name":"Department of Geriatrics, Gerontology Institute of Anhui Province, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolei","family":"Hao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Immune Response and Immunotherapy, Institute of Immunology, Biomedical Sciences and Health Laboratory of Anhui Province, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiming","family":"Wei","sequence":"additional","affiliation":[{"name":"Key Laboratory of Immune Response and Immunotherapy, Institute of Immunology, Biomedical Sciences and Health Laboratory of Anhui Province, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China"},{"name":"Research Unit of NK Cell Study, Chinese Academy of Medical Sciences, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Sun","sequence":"additional","affiliation":[{"name":"Key Laboratory of Immune Response and Immunotherapy, Institute of Immunology, Biomedical Sciences and Health Laboratory of Anhui Province, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China"},{"name":"Research Unit of NK Cell Study, Chinese Academy of Medical Sciences, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhigang","family":"Tian","sequence":"additional","affiliation":[{"name":"Key Laboratory of Immune Response and Immunotherapy, Institute of Immunology, Biomedical Sciences and Health Laboratory of Anhui Province, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China"},{"name":"Research Unit of NK Cell Study, Chinese Academy of Medical Sciences, Hefei 230027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"26","DOI":"10.2174\/1874357901812010026","article-title":"Epidemiology of Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) Related Hepatocellular Carcinoma","volume":"12","author":"Petruzziello","year":"2018","journal-title":"Open Virol. 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