Natural Killer Cells Regulate the Maturation of Liver Sinusoidal Endothelial Cells Thereby Promoting Intrahepatic T‐Cell Responses in a Mouse Model
Functional maturation of liver sinusoidal endothelial cells (LSECs) plays an important role in intrahepatic T‐cell activation and control of viral infections. Natural killer (NK) cells have been reported to prompt the maturation of antigen‐presenting cells (APCs), especially for dendritic cells (DCs...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer Health/LWW
2021-05-01
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| Series: | Hepatology Communications |
| Online Access: | https://doi.org/10.1002/hep4.1676 |
| _version_ | 1811173854453694464 |
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| author | Yanqin Du Hu Yan Shi Zou Tanvi Khera Jia Li Meihong Han Xiaoli Yang Baoju Wang Jia Liu Shuilin Sun Xin Zheng Ulf Dittmer Mengji Lu Dongliang Yang Heiner Wedemeyer Jun Wu |
| author_facet | Yanqin Du Hu Yan Shi Zou Tanvi Khera Jia Li Meihong Han Xiaoli Yang Baoju Wang Jia Liu Shuilin Sun Xin Zheng Ulf Dittmer Mengji Lu Dongliang Yang Heiner Wedemeyer Jun Wu |
| author_sort | Yanqin Du |
| collection | DOAJ |
| description | Functional maturation of liver sinusoidal endothelial cells (LSECs) plays an important role in intrahepatic T‐cell activation and control of viral infections. Natural killer (NK) cells have been reported to prompt the maturation of antigen‐presenting cells (APCs), especially for dendritic cells (DCs), but the interaction between NK cells and LSECs is elusive. Here, we investigated whether and how NK cells are involved in regulating LSEC maturation and if this has a role in controlling hepatitis B virus (HBV) infection in a mouse model. A chronic HBV replication mouse model was established by hydrodynamic injection (HI) of 6 µg adeno‐associated virus plasmid (pAAV)/HBV 1.2. The nucleotide‐binding oligomerization domain‐containing protein 1 (NOD1) ligand diaminopemelic acid (DAP) was imported into liver by HI at day 14 after plasmid injection. We found that HI of DAP recruited conventional NK cells (cNK) into the liver and promoted tumor necrosis factor alpha (TNF‐α) and interferon‐gamma (IFN‐γ) production of NK cells in a chemokine (C‐X‐C motif) receptor 3 (CXCR3)‐dependent manner. Importantly, the maturation of LSECs and the anti‐HBV effects of DAP were impaired in CXCR3−/− mice; this possibly was associated with the decreased number of intrahepatic cNK cells. Consistently, depleting cNK cells but not liver‐resident NK cells also impaired the maturation and antigen‐presenting function of LSECs, which reduced intrahepatic HBV‐specific T‐cell responses and thus inhibited HBV clearance both in wild‐type and in Rag1−/− mice. Moreover, TNF‐α or IFN‐γ stimulation as well as coculture with intrahepatic NK cells partly promoted LSEC phenotypic and functional maturation in vitro. Conclusion: NOD1‐triggered NK cell activation may lead to the enhancement of intrahepatic T‐cell responses by promoting maturation of LSECs through soluble cytokines and cell–cell contact, thereby controlling HBV replication and expression. |
| first_indexed | 2024-04-10T17:54:51Z |
| format | Article |
| id | doaj.art-315d984cc7f648d88bb98f3f243a8375 |
| institution | Directory Open Access Journal |
| issn | 2471-254X |
| language | English |
| last_indexed | 2024-04-10T17:54:51Z |
| publishDate | 2021-05-01 |
| publisher | Wolters Kluwer Health/LWW |
| record_format | Article |
| series | Hepatology Communications |
| spelling | doaj.art-315d984cc7f648d88bb98f3f243a83752023-02-02T18:58:53ZengWolters Kluwer Health/LWWHepatology Communications2471-254X2021-05-015586588110.1002/hep4.1676Natural Killer Cells Regulate the Maturation of Liver Sinusoidal Endothelial Cells Thereby Promoting Intrahepatic T‐Cell Responses in a Mouse ModelYanqin Du0Hu Yan1Shi Zou2Tanvi Khera3Jia Li4Meihong Han5Xiaoli Yang6Baoju Wang7Jia Liu8Shuilin Sun9Xin Zheng10Ulf Dittmer11Mengji Lu12Dongliang Yang13Heiner Wedemeyer14Jun Wu15Department of Infectious Diseases Union HospitalTongji Medical CollegeHuazhong University of Science and Technology Wuhan ChinaMucosal Immunity Research Group State Key Laboratory of Virology Wuhan Institute of VirologyChinese Academy of Sciences Wuhan ChinaDepartment of Infectious Diseases Union HospitalTongji Medical CollegeHuazhong University of Science and Technology Wuhan ChinaDepartment of Gastroenterology and Hepatology University Hospital of EssenUniversity of Duisburg‐Essen Essen GermanyDepartment of Infectious Diseases Union HospitalTongji Medical CollegeHuazhong University of Science and Technology Wuhan ChinaDepartment of Infectious Diseases Union HospitalTongji Medical CollegeHuazhong University of Science and Technology Wuhan ChinaDepartment of Infectious Diseases Union HospitalTongji Medical CollegeHuazhong University of Science and Technology Wuhan ChinaDepartment of Infectious Diseases Union HospitalTongji Medical CollegeHuazhong University of Science and Technology Wuhan ChinaDepartment of Infectious Diseases Union HospitalTongji Medical CollegeHuazhong University of Science and Technology Wuhan ChinaDepartment of Infectious Diseases the Second Affiliated Hospital of Nanchang University Nanchang ChinaDepartment of Infectious Diseases Union HospitalTongji Medical CollegeHuazhong University of Science and Technology Wuhan ChinaInstitute for Virology University Hospital of EssenUniversity of Duisburg‐Essen Essen GermanyInstitute for Virology University Hospital of EssenUniversity of Duisburg‐Essen Essen GermanyDepartment of Infectious Diseases Union HospitalTongji Medical CollegeHuazhong University of Science and Technology Wuhan ChinaDepartment of Gastroenterology and Hepatology University Hospital of EssenUniversity of Duisburg‐Essen Essen GermanyDepartment of Infectious Diseases Union HospitalTongji Medical CollegeHuazhong University of Science and Technology Wuhan ChinaFunctional maturation of liver sinusoidal endothelial cells (LSECs) plays an important role in intrahepatic T‐cell activation and control of viral infections. Natural killer (NK) cells have been reported to prompt the maturation of antigen‐presenting cells (APCs), especially for dendritic cells (DCs), but the interaction between NK cells and LSECs is elusive. Here, we investigated whether and how NK cells are involved in regulating LSEC maturation and if this has a role in controlling hepatitis B virus (HBV) infection in a mouse model. A chronic HBV replication mouse model was established by hydrodynamic injection (HI) of 6 µg adeno‐associated virus plasmid (pAAV)/HBV 1.2. The nucleotide‐binding oligomerization domain‐containing protein 1 (NOD1) ligand diaminopemelic acid (DAP) was imported into liver by HI at day 14 after plasmid injection. We found that HI of DAP recruited conventional NK cells (cNK) into the liver and promoted tumor necrosis factor alpha (TNF‐α) and interferon‐gamma (IFN‐γ) production of NK cells in a chemokine (C‐X‐C motif) receptor 3 (CXCR3)‐dependent manner. Importantly, the maturation of LSECs and the anti‐HBV effects of DAP were impaired in CXCR3−/− mice; this possibly was associated with the decreased number of intrahepatic cNK cells. Consistently, depleting cNK cells but not liver‐resident NK cells also impaired the maturation and antigen‐presenting function of LSECs, which reduced intrahepatic HBV‐specific T‐cell responses and thus inhibited HBV clearance both in wild‐type and in Rag1−/− mice. Moreover, TNF‐α or IFN‐γ stimulation as well as coculture with intrahepatic NK cells partly promoted LSEC phenotypic and functional maturation in vitro. Conclusion: NOD1‐triggered NK cell activation may lead to the enhancement of intrahepatic T‐cell responses by promoting maturation of LSECs through soluble cytokines and cell–cell contact, thereby controlling HBV replication and expression.https://doi.org/10.1002/hep4.1676 |
| spellingShingle | Yanqin Du Hu Yan Shi Zou Tanvi Khera Jia Li Meihong Han Xiaoli Yang Baoju Wang Jia Liu Shuilin Sun Xin Zheng Ulf Dittmer Mengji Lu Dongliang Yang Heiner Wedemeyer Jun Wu Natural Killer Cells Regulate the Maturation of Liver Sinusoidal Endothelial Cells Thereby Promoting Intrahepatic T‐Cell Responses in a Mouse Model Hepatology Communications |
| title | Natural Killer Cells Regulate the Maturation of Liver Sinusoidal Endothelial Cells Thereby Promoting Intrahepatic T‐Cell Responses in a Mouse Model |
| title_full | Natural Killer Cells Regulate the Maturation of Liver Sinusoidal Endothelial Cells Thereby Promoting Intrahepatic T‐Cell Responses in a Mouse Model |
| title_fullStr | Natural Killer Cells Regulate the Maturation of Liver Sinusoidal Endothelial Cells Thereby Promoting Intrahepatic T‐Cell Responses in a Mouse Model |
| title_full_unstemmed | Natural Killer Cells Regulate the Maturation of Liver Sinusoidal Endothelial Cells Thereby Promoting Intrahepatic T‐Cell Responses in a Mouse Model |
| title_short | Natural Killer Cells Regulate the Maturation of Liver Sinusoidal Endothelial Cells Thereby Promoting Intrahepatic T‐Cell Responses in a Mouse Model |
| title_sort | natural killer cells regulate the maturation of liver sinusoidal endothelial cells thereby promoting intrahepatic t cell responses in a mouse model |
| url | https://doi.org/10.1002/hep4.1676 |
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