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In a mouse model of influenza A virus (mouse adapted influenza A\/PR\/8\/34 strain) infection, long-term overexpression of IL-28B induced by hepatocyte-specific gene delivery exerted a strong antiviral effect in the presence of NK cells. In IL-28B\u2013overexpressing wild-type mice, the percentages and absolute numbers of NK cells in the spleen, liver, and lung were markedly increased, with higher proliferation and accelerated NK cell maturation based on phenotypes staining with CD11b and CD27 or CD11b and KLRG1. Furthermore, the effect of IL-28B on NK cells was macrophage dependent, as confirmed in an in vitro coculture assay and in in vivo macrophage- or alveolar macrophage\u2013depletion experiments. Transwell studies demonstrated that CFSE-labeled NK cell proliferation was driven, in a dose-dependent manner, by unknown soluble factor(s) secreted by IL-28B\u2013stimulated alveolar macrophages, without requiring direct cell\u2013cell contact. An understanding of the NK cell\u2013promoting features of IL-28B will facilitate future clinical application of this cytokine.<\/jats:p>","DOI":"10.4049\/jimmunol.1601430","type":"journal-article","created":{"date-parts":[[2017,6,22]],"date-time":"2017-06-22T00:30:32Z","timestamp":1498091432000},"page":"1012-1020","source":"Crossref","is-referenced-by-count":28,"title":["Involvement of NK Cells in IL-28B\u2013Mediated Immunity against Influenza Virus Infection"],"prefix":"10.1093","volume":"199","author":[{"given":"Yanshi","family":"Wang","sequence":"first","affiliation":[{"name":"Institute of Immunology, The Key Laboratory of Innate Immunity and Chronic Disease, Chinese Academy of Sciences, School of Life Sciences and Medical Center, University of Science and Technology of China , Hefei, Anhui 230027,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2754-9784","authenticated-orcid":false,"given":"Tingting","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Immunology, The Key Laboratory of Innate Immunity and Chronic Disease, Chinese Academy of Sciences, School of Life Sciences and Medical Center, University of Science and Technology of China , Hefei, Anhui 230027,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongyan","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Immunology, The Key Laboratory of Innate Immunity and Chronic Disease, Chinese Academy of Sciences, School of Life Sciences and Medical Center, University of Science and Technology of China , Hefei, Anhui 230027,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiming","family":"Wei","sequence":"additional","affiliation":[{"name":"Institute of Immunology, The Key Laboratory of Innate Immunity and Chronic Disease, Chinese Academy of Sciences, School of Life Sciences and Medical Center, University of Science and Technology of China , Hefei, Anhui 230027,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of Immunology, The Key Laboratory of Innate Immunity and Chronic Disease, Chinese Academy of Sciences, School of Life Sciences and Medical Center, University of Science and Technology of China , Hefei, Anhui 230027,","place":["China"]},{"name":"Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University , Hangzhou, Zhejiang 310003,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhigang","family":"Tian","sequence":"additional","affiliation":[{"name":"Institute of Immunology, The Key Laboratory of Innate Immunity and Chronic Disease, Chinese Academy of Sciences, School of Life Sciences and Medical Center, University of Science and Technology of China , Hefei, Anhui 230027,","place":["China"]},{"name":"Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University , Hangzhou, Zhejiang 310003,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,8,1]]},"reference":[{"key":"2025030614212853600_r1","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/ni875","article-title":"IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex","volume":"4","author":"Kotenko","year":"2003","journal-title":"Nat. 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