title: Innate immunity in the pathogenesis of cholangiopathy: a recent update.
abstract: Biliary innate immunity is involved in the pathogenesis of cholangiopathies in patients with various biliary diseases. Biliary epithelial cells possess an innate immune system consisting of the Toll-like receptor (TLR) family and recognize pathogen-associated molecular patterns (PAMPs). Recently, regulatory mechanisms by intracellular negative regulators including peroxisome proliferator-activated receptor-γ and micro-RNA have been clarified. In primary biliary cirrhosis (PBC) and primary sclerosing cholangitis, dysregulated biliary innate immunity, namely hyper-responsiveness to PAMPs, is associated with the histopathogenesis of cholangiopathy. Moreover, biliary epithelial cells produce monocyte chemotactic protein-1 (MCP-1/CCL2) as a result of the innate immune response and bile ductules play a role in hepatic fibrosis caused by hepatic stellate cells (HSCs). Also, biliary innate immune responses induce the production of two chemokines, fractalkine and macrophage inflammatory protein-3α (MIP-3α), causing the migration of inflammatory cells and a population of antigen-presenting cell found in epithelium, Langerhans cell, and involve chronic cholangitis associated with biliary epithelium-specific innate and acquired immunity in PBC.
authors.affiliation: Department of Human Pathology, Kanazawa University, Graduate School of Medicine, Kanazawa 920-8640, Japan. kenichih@med.kanazawa-u.ac.jp
authors.forename: Kenichi
authors.initials: K
authors.lastname: Harada
authors.forename: Yasuni
authors.initials: Y
authors.lastname: Nakanuma
mesh_terms: D001649:Bile Duct Diseases / Q000276:immunology* / Q000503:physiopathology; D001652:Bile Ducts / Q000166:cytology / Q000276:immunology / Q000503:physiopathology; D054418:Chemokine CCL20 / Q000378:metabolism; D054428:Chemokine CX3CL1 / Q000378:metabolism; D015209:Cholangitis, Sclerosing / Q000276:immunology / Q000503:physiopathology; D004847:Epithelial Cells / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D008103:Liver Cirrhosis / Q000276:immunology / Q000503:physiopathology; D008105:Liver Cirrhosis, Biliary / Q000276:immunology / Q000503:physiopathology; D051193:Toll-Like Receptors / Q000276:immunology*
chemical_list: D054418:Chemokine CCL20; D054428:Chemokine CX3CL1; D051193:Toll-Like Receptors