{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T14:14:06Z","timestamp":1783433646993,"version":"3.54.6"},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>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 \u03bcg 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-\u03b1) and interferon-gamma (IFN-\u03b3) 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<jats:sup>\u2212\/\u2212<\/jats:sup> 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<jats:sup>\u2212\/\u2212<\/jats:sup> mice. Moreover, TNF-\u03b1 or IFN-\u03b3 stimulation as well as coculture with intrahepatic NK cells partly promoted LSEC phenotypic and functional maturation <jats:italic toggle=\"yes\">in vitro<\/jats:italic>. <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> 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\u2013cell contact, thereby controlling HBV replication and expression.<\/jats:p>\n            <jats:p>NK cells promote intrahepatic T cell responses by regulating LSEC maturation. The potential mechanisms by which NK cells regulate the maturation of LSECs may involve soluble cytokines as well as cell-cell contact. The recruitment and activation of conventional NK cells (cNK) cells after NOD1 activation depend on CXCR3 axis.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep4.1676","type":"journal-article","created":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T06:21:41Z","timestamp":1612765301000},"page":"865-881","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":9,"title":["Natural Killer Cells Regulate the Maturation of Liver Sinusoidal Endothelial Cells Thereby Promoting Intrahepatic T-Cell Responses in a Mouse Model"],"prefix":"10.1097","volume":"5","author":[{"given":"Yanqin","family":"Du","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hu","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanvi","family":"Khera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meihong","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baoju","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuilin","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf","family":"Dittmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengji","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongliang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heiner","family":"Wedemeyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","container-title":["Hepatology Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hep4.1676","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/hep4.1676","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/10.1002\/hep4.1676","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T22:20:25Z","timestamp":1729030825000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/10.1002\/hep4.1676"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5]]},"references-count":0,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021]]}},"URL":"https:\/\/doi.org\/10.1002\/hep4.1676","relation":{},"ISSN":["2471-254X"],"issn-type":[{"value":"2471-254X","type":"print"}],"subject":[],"published":{"date-parts":[[2021,5]]}}}