NDLI: Natural killer cells promote long-term hepatobiliary inflammation in a low-dose rotavirus model of experimental biliary atresia.

Content Provider	Directory of Open Access Journals (DOAJ)
Author	James E. Squires Pranavkumar Shivakumar Reena Mourya Kazuhiko Bessho Stephanie Walters Jorge A. Bezerra
Abstract	Biliary atresia is a rapidly progressive obstructive cholangiopathy of infants. Mechanistic studies in the mouse model of Rhesus rotavirus (RRV)-induced biliary atresia have linked the importance of effector lymphocytes to the pathogenesis of extrahepatic bile duct (EHBD) injury and obstruction in experimental biliary atresia; however, studies of the progressive liver injury have been limited by early death of newborn mice. Here, we aimed to determine 1) if a lower inoculum of RRV induces obstruction of EHBDs while allowing for ongoing liver inflammation, and 2) if NK cells regulate intrahepatic injury. The administration of 0.25 x 10(6) fluorescence forming units of RRV induced an obstructive extrahepatic cholangiopathy, but allowed for restoration of the duct epithelium, increased survival, and the development of a progressive intrahepatic inflammatory injury with molecular and cellular signatures equivalent to the traditional infectious model. Investigating the mechanisms of liver injury, we found that NK cell depletion at the onset of jaundice decreased liver inflammation, suppressed the expression of fibrosis and inflammation/immunity genes, lowered plasma ALT and bilirubin and improved survival.Lower inoculation of RRV-induced progressive liver injury and fibrosis via NK cells. These findings point to the potential use of NK cell-depleting strategies to block progression of liver disease in biliary atresia.
e-ISSN	19326203
DOI	10.1371/journal.pone.0127191
Journal	PLoS ONE
Issue Number	5
Volume Number	10
Language	English
Publisher	Public Library of Science (PLoS)
Publisher Date	2015-01-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Medicine Science
Content Type	Text
Resource Type	Article

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