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Pediatric Surgery International

Erschienen in:

16.10.2017 | Review Article

Sclerosing and obstructive cholangiopathy in biliary atresia: mechanisms and association with biliary innate immunity

verfasst von: Kenichi Harada

Erschienen in: Pediatric Surgery International | Ausgabe 12/2017

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Abstract

Biliary atresia (BA) is histologically characterized by a progressive, sclerosing cholangitis and the obstruction of extrahepatic bile ducts. In terms of the etiology and pathogenesis of BA, several viral infections consisting of dsRNA, including Reoviridae, have been implicated. Human biliary epithelial cells (BECs) possess an innate immune system consisting of Toll-like receptors (TLRs). BECs have negative regulatory mechanisms of TLR tolerance to avoid an excessive inflammatory response to lipopolysaccharide (LPS), a TLR4 ligand; however, they lack the tolerance to poly(I:C) (a synthetic analog of viral dsRNA), a TLR3 ligand. Treatment with poly(I:C) induces the expression of the apoptosis-inducer TNF-related apoptosis-inducing ligand (TRAIL), along with the antiviral molecule IFN-β1, and reduces the viability of BECs by enhancing apoptosis. In response, surviving BECs increase their expression of various markers, including basic FGF [an epithelial–mesenchymal transition (EMT)-inducer], S100A4 (a mesenchymal marker), and Snail (a transcriptional factor), and decrease that of epithelial markers such as CK19 and E-cadherin before undergoing EMT. Extrahepatic bile ducts in BA infants frequently show a lack of epithelial markers and an aberrant expression of vimentin, in addition to the enhancement of TRAIL and apoptosis. dsRNA viruses may directly induce apoptosis and EMT in human BECs as a result of the biliary innate immune response, supporting the notion that Reoviridae infections may be directly associated with the pathogenesis of cholangiopathies in BA.

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Titel: Sclerosing and obstructive cholangiopathy in biliary atresia: mechanisms and association with biliary innate immunity
verfasst von: Kenichi Harada
Publikationsdatum: 16.10.2017
Verlag: Springer Berlin Heidelberg
Erschienen in: Pediatric Surgery International / Ausgabe 12/2017
Print ISSN: 0179-0358
Elektronische ISSN: 1437-9813
DOI: https://doi.org/10.1007/s00383-017-4154-8

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