{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T11:17:24Z","timestamp":1776424644184,"version":"3.51.2"},"reference-count":78,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Liver diseases, ranging from chronic hepatitis and metabolic dysfunction to cirrhosis and hepatocellular carcinoma, represent a major global public health burden. As an immune-privileged organ, the liver harbors a unique and intricate immune microenvironment, which plays a dual role in pathogen clearance and chronicity. Kupffer cells (KCs), the primary resident macrophages in the liver, constitute the first line of defense in liver innate immunity and play complex and important roles in pathogen recognition, phagocytosis, and the regulation of liver inflammation and immune responses. The complement receptor of the immunoglobulin superfamily (CRIg) is a membrane receptor that is specifically expressed on KCs. It serves not only as a sentinel for the liver against pathogen invasion but also as a sophisticated regulator for maintaining immune homeostasis. As a key component of the liver\u2019s immune system, CRIg can efficiently mediate the clearance of complement-opsonized particles, thereby playing multidimensional roles in pathogen clearance, antigen cross-presentation, and the establishment of immune tolerance, functioning as both a \u201cpathogen catcher\u201d and an \u201cimmune brake.\u201d This review focuses on the CRIg molecule, detailing its mechanisms in the recognition and phagocytic clearance by KCs, and its subsequent impact on hepatic immune responses. Furthermore, we explored the potential involvement of CRIg in the pathological progression of diverse liver diseases, including persistent inflammation, fibrosis, and hepatocarcinogenesis. This synthesis provides novel insights into the immunopathology of liver diseases and establishes a theoretical foundation for developing CRIg-targeted therapeutic strategies.<\/jats:p>","DOI":"10.3390\/v18040473","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T10:11:04Z","timestamp":1776420664000},"page":"473","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Key Role of Complement Receptor CRIg in Kupffer Cell-Mediated Liver Disease Progression"],"prefix":"10.3390","volume":"18","author":[{"given":"Xin-Zhou","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Anaesthesia, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Blood Transfusion, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e362","DOI":"10.1016\/S1473-3099(24)00307-4","article-title":"WHO\u2019s 2024 global hepatitis report","volume":"24","author":"Burki","year":"2024","journal-title":"Lancet Infect. 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