CRIg on liver macrophages clears pathobionts and protects against alcoholic liver disease

Yi Duan, Huikuan Chu, Katharina Brandl, Lu Jiang, Suling Zeng, Nairika Meshgin, Eleni Papachristoforou, Josepmaria Argemi, Beatriz G. Mendes, Yanhan Wang, Hua Su, Weizhong Sun, Cristina Llorente, Tim Hendrikx, Xiao Liu, Mojgan Hosseini, Tatiana Kisseleva, David A. Brenner, Ramon Bataller, Prakash RamachandranMichael Karin, Wenxian Fu, Bernd Schnabl

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Complement receptor of immunoglobulin superfamily (CRIg) is expressed on liver macrophages and directly binds complement component C3b or Gram-positive bacteria to mediate phagocytosis. CRIg plays important roles in several immune-mediated diseases, but it is not clear how its pathogen recognition and phagocytic functions maintain homeostasis and prevent disease. We previously associated cytolysin-positive Enterococcus faecalis with severity of alcohol-related liver disease. Here, we demonstrate that CRIg is reduced in liver tissues from patients with alcohol-related liver disease. CRIg-deficient mice developed more severe ethanol-induced liver disease than wild-type mice; disease severity was reduced with loss of toll-like receptor 2. CRIg-deficient mice were less efficient than wild-type mice at clearing Gram-positive bacteria such as Enterococcus faecalis that had translocated from gut to liver. Administration of the soluble extracellular domain CRIg–Ig protein protected mice from ethanol-induced steatohepatitis. Our findings indicate that ethanol impairs hepatic clearance of translocated pathobionts, via decreased hepatic CRIg, which facilitates progression of liver disease.
Original languageEnglish
JournalNature Communications
Issue number1
Publication statusPublished - 9 Dec 2021


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