Affiliation:
1. Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana
2. Department of Research, Richard L. Roudebush VA Medical Center, Indianapolis, Indiana
Abstract
Mast cells (MCs) contribute to the pathogenesis of cholestatic liver diseases (primary sclerosing cholangitis [PSC] and primary biliary cholangitis [PBC]). PSC and PBC are immune-mediated, chronic inflammatory diseases, characterized by bile duct inflammation and stricturing, advancing to hepatobiliary cirrhosis. MCs are tissue resident immune cells that may promote hepatic injury, inflammation, and fibrosis formation by either direct or indirect interactions with other innate immune cells (neutrophils, macrophages/Kupffer cells, dendritic cells, natural killer, and innate lymphoid cells). The activation of these innate immune cells, usually through the degranulation of MCs, promotes antigen uptake and presentation to adaptive immune cells, exacerbating liver injury. In conclusion, dysregulation of MC-innate immune cell communications during liver injury and inflammation can lead to chronic liver injury and cancer.
Funder
Hickam Endowed Chair, Gastroenterology, Medicine, Indiana University, the Indiana University Health – Indiana University School of Medicine Strategic Research Initiative
United States Department of Veteran's Affairs, Biomedical Laboratory Research and Development Service
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