Cargando…
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....
Autores principales: | , , , , , , , , , , , |
---|---|
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 |
_version_ | 1783260980363395072 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5581021 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT fuqiuxia hepaticnkcellmediatedhypersensitivitytoconainducedliverinjuryinmouseliverexpressinghepatitiscviruspolyprotein AT yanshaoduo hepaticnkcellmediatedhypersensitivitytoconainducedliverinjuryinmouseliverexpressinghepatitiscviruspolyprotein AT wanglicui hepaticnkcellmediatedhypersensitivitytoconainducedliverinjuryinmouseliverexpressinghepatitiscviruspolyprotein AT duanxiangguo hepaticnkcellmediatedhypersensitivitytoconainducedliverinjuryinmouseliverexpressinghepatitiscviruspolyprotein AT wanglei hepaticnkcellmediatedhypersensitivitytoconainducedliverinjuryinmouseliverexpressinghepatitiscviruspolyprotein AT wangyue hepaticnkcellmediatedhypersensitivitytoconainducedliverinjuryinmouseliverexpressinghepatitiscviruspolyprotein AT wutao hepaticnkcellmediatedhypersensitivitytoconainducedliverinjuryinmouseliverexpressinghepatitiscviruspolyprotein AT wangxiaohui hepaticnkcellmediatedhypersensitivitytoconainducedliverinjuryinmouseliverexpressinghepatitiscviruspolyprotein AT anjie hepaticnkcellmediatedhypersensitivitytoconainducedliverinjuryinmouseliverexpressinghepatitiscviruspolyprotein AT zhangyulong hepaticnkcellmediatedhypersensitivitytoconainducedliverinjuryinmouseliverexpressinghepatitiscviruspolyprotein AT zhouqianqian hepaticnkcellmediatedhypersensitivitytoconainducedliverinjuryinmouseliverexpressinghepatitiscviruspolyprotein AT zhanlinsheng hepaticnkcellmediatedhypersensitivitytoconainducedliverinjuryinmouseliverexpressinghepatitiscviruspolyprotein |