Innate Immunity in the Pathogenesis of Cholangiopathy: A Recent Update

Author(s): Kenichi Harada, Yasuni Nakanuma

Journal Name: Inflammation & Allergy - Drug Targets (Discontinued)
Formerly Current Drug Targets - Inflammation & Allergy

Volume 11 , Issue 6 , 2012


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.

Keywords: Biliary epithelial cell, chemokine, cholangiopathy, innate immunity, primary biliary cirrhosis, Toll-like receptor, Biliary innate immunity, hepatic fibrosis, Ductular reaction, primary biliary cirrhosis, Fractalkine

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2012
Published on: 22 October, 2012
Page: [478 - 483]
Pages: 6
DOI: 10.2174/187152812803589976
Price: $65

Article Metrics

PDF: 26