Natural killer cells promote long-term hepatobiliary inflammation in a low-dose rotavirus model of experimental biliary atresia.
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 e...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4437784?pdf=render |
| _version_ | 1819263900882829312 |
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| author | James E Squires Pranavkumar Shivakumar Reena Mourya Kazuhiko Bessho Stephanie Walters Jorge A Bezerra |
| author_facet | James E Squires Pranavkumar Shivakumar Reena Mourya Kazuhiko Bessho Stephanie Walters Jorge A Bezerra |
| author_sort | James E Squires |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-23T20:20:57Z |
| format | Article |
| id | doaj.art-c8170816948d45b3a6c031b102ac86cb |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T20:20:57Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-c8170816948d45b3a6c031b102ac86cb2022-12-21T17:32:32ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01105e012719110.1371/journal.pone.0127191Natural killer cells promote long-term hepatobiliary inflammation in a low-dose rotavirus model of experimental biliary atresia.James E SquiresPranavkumar ShivakumarReena MouryaKazuhiko BesshoStephanie WaltersJorge A BezerraBiliary 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.http://europepmc.org/articles/PMC4437784?pdf=render |
| spellingShingle | James E Squires Pranavkumar Shivakumar Reena Mourya Kazuhiko Bessho Stephanie Walters Jorge A Bezerra Natural killer cells promote long-term hepatobiliary inflammation in a low-dose rotavirus model of experimental biliary atresia. PLoS ONE |
| title | Natural killer cells promote long-term hepatobiliary inflammation in a low-dose rotavirus model of experimental biliary atresia. |
| title_full | Natural killer cells promote long-term hepatobiliary inflammation in a low-dose rotavirus model of experimental biliary atresia. |
| title_fullStr | Natural killer cells promote long-term hepatobiliary inflammation in a low-dose rotavirus model of experimental biliary atresia. |
| title_full_unstemmed | Natural killer cells promote long-term hepatobiliary inflammation in a low-dose rotavirus model of experimental biliary atresia. |
| title_short | Natural killer cells promote long-term hepatobiliary inflammation in a low-dose rotavirus model of experimental biliary atresia. |
| title_sort | natural killer cells promote long term hepatobiliary inflammation in a low dose rotavirus model of experimental biliary atresia |
| url | http://europepmc.org/articles/PMC4437784?pdf=render |
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