title: Periductal interleukin-17 production in association with biliary innate immunity contributes to the pathogenesis of cholangiopathy in primary biliary cirrhosis.
abstract: An innate immune response to bacterial components is speculated to be involved in the pathogenesis of primary biliary cirrhosis (PBC). Recently, CD4-positive T helper type 17 (Th17) cells, characterized by the secretion of interleukin (IL)-17, have been implicated in the pathogenesis of autoimmune diseases. Human Th17 cells are generated from Th0 cells by IL-6 and IL-1 beta and maintained by IL-23. In this study, the role of IL-17 in PBC and its association with biliary innate immunity were examined. Using cultured human biliary epithelial cells (BECs), the expression of Th17-related cytokines and chemokines and changes therein on treatment with pathogen-associated molecular patterns (PAMPs) and IL-17 were examined. Immunohistochemistry for IL-17 and Th17-related cytokines was performed using tissue samples of human liver. Consequently, the expression of IL-6, IL-1 beta, IL-23p19 and IL-23/IL-12p40 mRNAs, and their up-regulation by PAMPs, were found in BECs. Moreover, BECs possessed IL-17-receptors and stimulation with IL-17 induced production of IL-6, IL-1 beta, IL-23p19 and chemokines. Several IL-17-positive cells had infiltrated damaged bile ducts and the expression of IL-6 and IL-1 beta was enhanced in the bile ducts of PBC patients. In conclusion, IL-17-positive cells are associated with the chronic inflammation of bile ducts in PBC which is associated causally with the biliary innate immune responses to PAMPs.
authors: Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
authors: K
authors: K
authors: Harada
authors: S
authors: S
authors: Shimoda
authors: Y
authors: Y
authors: Sato
authors: K
authors: K
authors: Isse
authors: H
authors: H
authors: Ikeda
authors: Y
authors: Y
authors: Nakanuma
mesh_terms: D001327:Autoimmune Diseases / Q000276:immunology*; D001653:Bile Ducts, Intrahepatic / Q000276:immunology; D001659:Biliary Tract / Q000276:immunology*; D016022:Case-Control Studies; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007113:Immunity, Innate; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000032:analysis* / Q000235:genetics / Q000494:pharmacology; D007378:Interleukins / Q000235:genetics / Q000276:immunology; D008105:Liver Cirrhosis, Biliary / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D020381:Interleukin-17; D007378:Interleukins; D012333:RNA, Messenger