{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T07:53:17Z","timestamp":1787125997583,"version":"build-2736575974"},"reference-count":48,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T00:00:00Z","timestamp":1696896000000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Available therapies for chronic hepatitis B virus (HBV) infection are not satisfying, and interleukin\u201021 (IL\u201021) and checkpoint inhibitors are potential therapeutic options. However, the mechanism underlying IL\u201021 and checkpoint inhibitors in treating chronic HBV infection is unclear. To explore whether IL\u201021 and checkpoint inhibitors promote HBV clearance by modulating the function of natural killer (NK) cells, we measured the phenotypes and functions of NK cells in chronic HBV\u2010infected patients and healthy controls on mRNA and protein levels. We found that chronic HBV infection disturbed the transcriptome of NK cells, including decreased expression of\n                    <jats:italic>KLRK1, TIGIT, GZMA, PRF1<\/jats:italic>\n                    , and increased expression of\n                    <jats:italic>CD69<\/jats:italic>\n                    . We also observed altered phenotypes and functions of NK cells in chronic HBV\u2010infected patients, characterized by decreased NKG2D expression, increased TIGIT expression and impaired interferon\u2010gamma (IFN\u2010\u03b3), tumor necrosis factor\u2010alpha (TNF\u2010\u03b1) production. Furthermore, these alterations cannot be restored by telbivudine treatment but can be partially restored by IL\u201021 and anti\u2010TIGIT stimulation. IL\u201021 upregulated the expression of activating receptor CD16, CD69, and NKG2D on NK cells, enhanced IFN\u2010\u03b3 production, cytolysis, and proliferation of NK cells, while anti\u2010TIGIT promoted IFN\u2010\u03b3 production in CD56\n                    <jats:sup>dim<\/jats:sup>\n                    subset exclusively in chronic HBV infected patients. Additionally, IL\u201021 was indispensable for anti\u2010TIGIT in HBsAg clearance in mice bearing HBV. It enhanced IFN\u2010\u03b3 production in splenic NK cells rather than intrahepatic NK cells, indicating a brand\u2010new mechanism of IL\u201021 in HBV clearance when combined with anti\u2010TIGIT. Overall, our findings contribute to the design of immunotherapy through enhancing the antiviral efficacy of NK cells in chronic HBV infection.\n                  <\/jats:p>","DOI":"10.1002\/jmv.29142","type":"journal-article","created":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T23:37:23Z","timestamp":1697067443000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["IL\u201021 collaborates with anti\u2010TIGIT to restore NK cell function in chronic HBV infection"],"prefix":"10.1002","volume":"95","author":[{"given":"Libo","family":"Tang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital Southern Medical University  Guangzhou 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