Preferential TNFα signaling via TNFR2 regulates epithelial injury and duct obstruction in experimental biliary atresia.

ABSTRACT: Biliary atresia is an obstructive cholangiopathy of infancy that progresses to end-stage cirrhosis. Although the pathogenesis of the disease is not completely understood, previous reports link TNFα to apoptosis of the bile duct epithelium in the presence of IFNγ. Here, we investigate if TNFα signaling regulates pathogenic mechanisms of biliary atresia. First, we quantified the expression of TNFA and its receptors TNFR1 and TNFR2 in human livers and found an increased expression of the receptors at the time of diagnosis. In mechanistic experiments using a neonatal mouse model of rhesus rotavirus-induced (RRV-induced) biliary atresia, the expression of the ligand and both receptors increased 6- to 8-fold in hepatic DCs and NK lymphocytes above controls. The activation of

SUBMITTER: Shivakumar P 

PROVIDER: S-EPMC5333971 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature