{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T16:07:01Z","timestamp":1771862821443,"version":"3.50.1"},"reference-count":60,"publisher":"American Physiological Society","issue":"5","funder":[{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17K16060"],"award-info":[{"award-number":["17K16060"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18J12875"],"award-info":[{"award-number":["18J12875"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP18H02821"],"award-info":[{"award-number":["JP18H02821"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP18K19566"],"award-info":[{"award-number":["JP18K19566"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.physiology.org"],"crossmark-restriction":true},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2021,11,1]]},"abstract":"<jats:p> The influenza virus infection poses a serious health threat worldwide. Myeloid cells play pivotal roles in regulating innate and adaptive immune defense. A disintegrin and metalloproteinase (ADAM) family of proteins contributes to various immune responses; however, the role of a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) in influenza virus infection remains largely unknown. Herein, we investigated its role, focusing on myeloid cells, during influenza virus infection in mice. ADAM10 gene ( Adam10) <jats:sup>flox\/flox<\/jats:sup>\/Lyz2-Cre ( Adam10<jats:sup>\u0394Lyz2<\/jats:sup>) and control Adam10<jats:sup>flox\/flox<\/jats:sup> mice were intranasally infected with 200 plaque-forming units of influenza virus A\/H1N1\/PR8\/34. Adam10<jats:sup>\u0394Lyz2<\/jats:sup> mice exhibited a significantly higher mortality rate, stronger lung inflammation, and a higher virus titer in the lungs than control mice. Macrophages and inflammatory cytokines, such as TNF-\u03b1, IL-1\u03b2, and CCL2, were increased in bronchoalveolar lavage fluid from Adam10<jats:sup>\u0394Lyz2<\/jats:sup> mice following infection. CD11b<jats:sup>+<\/jats:sup>Ly6G<jats:sup>\u2013<\/jats:sup>F4\/80<jats:sup>+<\/jats:sup> myeloid cells, which had an inflammatory monocyte\/macrophage-like phenotype, were significantly increased in the lungs of Adam10<jats:sup>\u0394Lyz2<\/jats:sup> mice. Adoptive transfer experiments suggested that these cells likely contributed to the poorer prognosis in Adam10<jats:sup>\u0394Lyz2<\/jats:sup> mice. Seven days after infection, CD11b<jats:sup>+<\/jats:sup>Ly6G<jats:sup>\u2013<\/jats:sup>F4\/80<jats:sup>+<\/jats:sup> lung cells exhibited significantly higher arginase-1 expression levels in Adam10<jats:sup>\u0394Lyz2<\/jats:sup> mice than in control mice, whereas an arginase-1 inhibitor improved the prognosis of Adam10<jats:sup>\u0394Lyz2<\/jats:sup> mice. Enhanced granulocyte-macrophage colony-stimulating factor (GM-CSF)\/GM-CSF receptor signaling likely contributed to this process. Collectively, these results indicate that myeloid ADAM10 protects against influenza virus pneumonia and may be a promising therapeutic target. <\/jats:p>","DOI":"10.1152\/ajplung.00619.2020","type":"journal-article","created":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T12:01:18Z","timestamp":1631707278000},"page":"L872-L884","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["ADAM10 partially protects mice against influenza pneumonia by suppressing specific myeloid cell population"],"prefix":"10.1152","volume":"321","author":[{"given":"Satoshi","family":"Okamori","sequence":"first","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan"},{"name":"Japan Society of Promotion of Science, Tokyo, 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