{"title":"CD96 enhances the anti-viral activity of natural killer cells by promoting Ly49H-mediated activation during mouse cytomegalovirus infection","authors":"Soichi Matsuo , Tsukasa Nabekura , Kazuko Shibuya , Akira Shibuya","doi":"10.1016/j.molimm.2025.02.001","DOIUrl":null,"url":null,"abstract":"<div><div>Natural killer (NK) cells are cytotoxic innate lymphocytes that play a critical role in controlling viral infections. Although CD96 has been reported as an immune checkpoint molecule in tumor immunity, the role of CD96 in NK cell activity in viral infections remains undetermined. Here, we demonstrate that CD96 functions as an activating receptor on NK cells in mouse cytomegalovirus (MCMV) infection. CD96-deficient (<em>Cd96</em><sup>-/-</sup>) mice exhibited a high MCMV burden, as compared with wild-type (WT) mice. CD96 augmented the effector function of NK cells expressing Ly49H, an activating NK receptor specific for the MCMV m157 protein, against m157-expressing target cells <em>in vitro</em>. Mechanistically, CD96 maintained the Ly49H-mediated phosphorylation of the protein tyrosine kinases Zap70 and or Syk. These findings suggest that CD96 enhances the anti-viral activity of Ly49H<sup>+</sup> NK cells against MCMV infection.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"179 ","pages":"Pages 65-70"},"PeriodicalIF":3.2000,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular immunology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0161589025000252","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Natural killer (NK) cells are cytotoxic innate lymphocytes that play a critical role in controlling viral infections. Although CD96 has been reported as an immune checkpoint molecule in tumor immunity, the role of CD96 in NK cell activity in viral infections remains undetermined. Here, we demonstrate that CD96 functions as an activating receptor on NK cells in mouse cytomegalovirus (MCMV) infection. CD96-deficient (Cd96-/-) mice exhibited a high MCMV burden, as compared with wild-type (WT) mice. CD96 augmented the effector function of NK cells expressing Ly49H, an activating NK receptor specific for the MCMV m157 protein, against m157-expressing target cells in vitro. Mechanistically, CD96 maintained the Ly49H-mediated phosphorylation of the protein tyrosine kinases Zap70 and or Syk. These findings suggest that CD96 enhances the anti-viral activity of Ly49H+ NK cells against MCMV infection.
期刊介绍：
Molecular Immunology publishes original articles, reviews and commentaries on all areas of immunology, with a particular focus on description of cellular, biochemical or genetic mechanisms underlying immunological phenomena. Studies on all model organisms, from invertebrates to humans, are suitable. Examples include, but are not restricted to:
Infection, autoimmunity, transplantation, immunodeficiencies, inflammation and tumor immunology
Mechanisms of induction, regulation and termination of innate and adaptive immunity
Intercellular communication, cooperation and regulation
Intracellular mechanisms of immunity (endocytosis, protein trafficking, pathogen recognition, antigen presentation, etc)
Mechanisms of action of the cells and molecules of the immune system
Structural analysis
Development of the immune system
Comparative immunology and evolution of the immune system
"Omics" studies and bioinformatics
Vaccines, biotechnology and therapeutic manipulation of the immune system (therapeutic antibodies, cytokines, cellular therapies, etc)
Technical developments.
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