Neonatal NK cells target the mouse duct epithelium via Nkg2d and drive tissue-specific injury in experimental biliary atresia

摘要: Biliary atresia is a neonatal obstructive cholangiopathy that progresses to end-stage liver disease. Although the etiology unknown, adaptive immune signature has been mechanistically linked obstruction of extrahepatic bile ducts. Here, we investigated role innate response in pathogenesis biliary atresia. Analysis livers infants at diagnosis revealed NK cells populate vicinity intrahepatic ducts and overexpress several genes involved cytotoxicity. Using model rotavirus-induced newborn mice, found activated also populated murine were most abundant time obstruction. Rotavirus-primed hepatic lysed cholangiocytes contact- Nkg2d-dependent fashion. Depletion blockade Nkg2d each prevented injury duct epithelium after rotavirus infection, maintained continuity lumen between duodenum, enabled flow, despite presence virus tissue overexpression proinflammatory cytokines. These findings identify as key initiators cholangiocyte via demonstrate drives phenotype experimental