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Hepatic NK cell-mediated hypersensitivity to ConA-induced liver injury in mouse liver expressing hepatitis C virus polyprotein

The role of hepatic NK cells in the pathogenesis of HCV-associated hepatic failure is incompletely understood. In this study, we investigated the effect of HCV on ConA-induced immunological hepatic injury and the influence of HCV on hepatic NK cell activation in the liver after ConA administration....

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Autores principales: Fu, Qiuxia, Yan, Shaoduo, Wang, Licui, Duan, Xiangguo, Wang, Lei, Wang, Yue, Wu, Tao, Wang, Xiaohui, An, Jie, Zhang, Yulong, Zhou, Qianqian, Zhan, Linsheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5581021/
https://www.ncbi.nlm.nih.gov/pubmed/28881722
http://dx.doi.org/10.18632/oncotarget.11052
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author Fu, Qiuxia
Yan, Shaoduo
Wang, Licui
Duan, Xiangguo
Wang, Lei
Wang, Yue
Wu, Tao
Wang, Xiaohui
An, Jie
Zhang, Yulong
Zhou, Qianqian
Zhan, Linsheng
author_facet Fu, Qiuxia
Yan, Shaoduo
Wang, Licui
Duan, Xiangguo
Wang, Lei
Wang, Yue
Wu, Tao
Wang, Xiaohui
An, Jie
Zhang, Yulong
Zhou, Qianqian
Zhan, Linsheng
author_sort Fu, Qiuxia
collection PubMed
description The role of hepatic NK cells in the pathogenesis of HCV-associated hepatic failure is incompletely understood. In this study, we investigated the effect of HCV on ConA-induced immunological hepatic injury and the influence of HCV on hepatic NK cell activation in the liver after ConA administration. An immunocompetent HCV mouse model that encodes the entire viral polyprotein in a liver-specific manner based on hydrodynamic injection and φC31o integrase was used to study the role of hepatic NK cells. Interestingly, the frequency of hepatic NK cells was reduced in HCV mice, whereas the levels of other intrahepatic lymphocytes remained unaltered. Next, we investigated whether the reduction in NK cells within HCV mouse livers might elicit an effect on immune-mediated liver injury. HCV mice were subjected to acute liver injury models upon ConA administration. We observed that HCV mice developed more severe ConA-induced immune-mediated hepatitis, which was dependent on the accumulated intrahepatic NK cells. Our results indicated that after the administration of ConA, NK cells not only mediated liver injury through the production of immunoregulatory cytokines (IFN-γ, TNF-α and perforin) with direct antiviral activity, but they also killed target cells directly through the TRAIL/DR5 and NKG2D/NKG2D ligand signaling pathway in HCV mice. Our findings suggest a critical role for NK cells in oversensitive liver injury during chronic HCV infection.
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spelling pubmed-55810212017-09-06 Hepatic NK cell-mediated hypersensitivity to ConA-induced liver injury in mouse liver expressing hepatitis C virus polyprotein Fu, Qiuxia Yan, Shaoduo Wang, Licui Duan, Xiangguo Wang, Lei Wang, Yue Wu, Tao Wang, Xiaohui An, Jie Zhang, Yulong Zhou, Qianqian Zhan, Linsheng Oncotarget Research Paper The role of hepatic NK cells in the pathogenesis of HCV-associated hepatic failure is incompletely understood. In this study, we investigated the effect of HCV on ConA-induced immunological hepatic injury and the influence of HCV on hepatic NK cell activation in the liver after ConA administration. An immunocompetent HCV mouse model that encodes the entire viral polyprotein in a liver-specific manner based on hydrodynamic injection and φC31o integrase was used to study the role of hepatic NK cells. Interestingly, the frequency of hepatic NK cells was reduced in HCV mice, whereas the levels of other intrahepatic lymphocytes remained unaltered. Next, we investigated whether the reduction in NK cells within HCV mouse livers might elicit an effect on immune-mediated liver injury. HCV mice were subjected to acute liver injury models upon ConA administration. We observed that HCV mice developed more severe ConA-induced immune-mediated hepatitis, which was dependent on the accumulated intrahepatic NK cells. Our results indicated that after the administration of ConA, NK cells not only mediated liver injury through the production of immunoregulatory cytokines (IFN-γ, TNF-α and perforin) with direct antiviral activity, but they also killed target cells directly through the TRAIL/DR5 and NKG2D/NKG2D ligand signaling pathway in HCV mice. Our findings suggest a critical role for NK cells in oversensitive liver injury during chronic HCV infection. Impact Journals LLC 2016-08-04 /pmc/articles/PMC5581021/ /pubmed/28881722 http://dx.doi.org/10.18632/oncotarget.11052 Text en Copyright: © 2017 Fu et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper
Fu, Qiuxia
Yan, Shaoduo
Wang, Licui
Duan, Xiangguo
Wang, Lei
Wang, Yue
Wu, Tao
Wang, Xiaohui
An, Jie
Zhang, Yulong
Zhou, Qianqian
Zhan, Linsheng
Hepatic NK cell-mediated hypersensitivity to ConA-induced liver injury in mouse liver expressing hepatitis C virus polyprotein
title Hepatic NK cell-mediated hypersensitivity to ConA-induced liver injury in mouse liver expressing hepatitis C virus polyprotein
title_full Hepatic NK cell-mediated hypersensitivity to ConA-induced liver injury in mouse liver expressing hepatitis C virus polyprotein
title_fullStr Hepatic NK cell-mediated hypersensitivity to ConA-induced liver injury in mouse liver expressing hepatitis C virus polyprotein
title_full_unstemmed Hepatic NK cell-mediated hypersensitivity to ConA-induced liver injury in mouse liver expressing hepatitis C virus polyprotein
title_short Hepatic NK cell-mediated hypersensitivity to ConA-induced liver injury in mouse liver expressing hepatitis C virus polyprotein
title_sort hepatic nk cell-mediated hypersensitivity to cona-induced liver injury in mouse liver expressing hepatitis c virus polyprotein
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5581021/
https://www.ncbi.nlm.nih.gov/pubmed/28881722
http://dx.doi.org/10.18632/oncotarget.11052
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