Biliary innate immunity: function and modulation.
Biliary innate immunity is involved in the pathogenesis of cholangiopathies in patients with primary biliary cirrhosis (PBC) and biliary atresia. Biliary epithelial cells possess an innate immune system consisting of the Toll-like receptor (TLR) family and recognize pathogen-associated molecular patterns (PAMPs). Tolerance to bacterial PAMPs such as lipopolysaccharides is also important to maintain homeostasis in the biliary tree, but tolerance to double-stranded RNA (dsRNA) is not found. In PBC, CD4-positive Th17 cells characterized by the secretion of IL-17 are implicated in the chronic inflammation of bile ducts and the presence of Th17 cells around bile ducts is causally associated with the biliary innate immune responses to PAMPs. Moreover, a negative regulator of intracellular TLR signaling, peroxisome proliferator-activated receptor-gamma (PPARgamma), is involved in the pathogenesis of cholangitis. Immunosuppression using PPARgamma ligands may help to attenuate the bile duct damage in PBC patients. In biliary atresia characterized by a progressive, inflammatory, and sclerosing cholangiopathy, dsRNA viruses are speculated to be an etiological agent and to directly induce enhanced biliary apoptosis via the expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Moreover, the epithelial-mesenchymal transition (EMT) of biliary epithelial cells is also evoked by the biliary innate immune response to dsRNA.
Harada
Kenichi
K
Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan. kenichih@med.kanazawa-u.ac.jp
Nakanuma
Yasuni
Y
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001656:Biliary Atresia / Q000276:immunology* / Q000473:pathology; D001659:Biliary Tract / Q000276:immunology*; D002761:Cholangitis / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D023082:Defensins / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D042882:Gallstones / Q000276:immunology / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate; D008105:Liver Cirrhosis, Biliary / Q000276:immunology* / Q000473:pathology; D047495:PPAR gamma / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology
D000942:Antigens, Bacterial; D016207:Cytokines; D023082:Defensins; D047495:PPAR gamma; D051193:Toll-Like Receptors
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