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In response to severe influenza virus infection, adoptively transferred na\u00efve hemagglutinin-specific CD4<jats:sup>+<\/jats:sup> T cells from CD4<jats:sup>+<\/jats:sup> TCR-transgenic 6.5 mice drive an IFN-\u03b3-producing Th1 response in wild-type mice. It helps in virus clearance but also causes collateral damage and disease aggravation. The donor 6.5 mice have all the CD4<jats:sup>+<\/jats:sup> T cells with TCR specificity toward influenza hemagglutinin. Still, the infected 6.5 mice do not suffer from robust inflammation and grave outcome. The initial Th1 response wanes with time, and a prominent Th17 response of recent thymic emigrants alleviates inflammation and bestows protection in 6.5 mice. Our results suggest that viral neuraminidase-activated TGF-\u03b2 of the Th1 cells guides the Th17 evolution, and IL-17 signaling through the non-canonical IL-17 receptor EGFR activates the scaffold protein TRAF4 more than TRAF6 during alleviation of lung inflammation in severe influenza.<\/jats:p>","DOI":"10.1038\/s42003-023-04982-0","type":"journal-article","created":{"date-parts":[[2023,6,3]],"date-time":"2023-06-03T10:01:41Z","timestamp":1685786501000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["An IL-17-EGFR-TRAF4 axis contributes to the alleviation of lung inflammation in severe influenza"],"prefix":"10.1038","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5372-629X","authenticated-orcid":false,"given":"Avijit","family":"Dutta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-Yiu","family":"Hung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2532-7328","authenticated-orcid":false,"given":"Tse-Ching","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Han","family":"Hsiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Shiang","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yung-Chang","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3007-3190","authenticated-orcid":false,"given":"Chun-Yen","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8624-4513","authenticated-orcid":false,"given":"Ching-Tai","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,6,3]]},"reference":[{"key":"4982_CR1","doi-asserted-by":"publisher","first-page":"2255","DOI":"10.1056\/NEJMra2026131","volume":"383","author":"DC Fajgenbaum","year":"2020","unstructured":"Fajgenbaum, D. 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