{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T01:51:19Z","timestamp":1792461079510,"version":"4.5.0"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2017,9,1]],"date-time":"2017-09-01T00:00:00Z","timestamp":1504224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Members of the IL-1 family play protective and regulatory roles in immune defense against the opportunistic mold Aspergillus fumigatus. In this study, we investigated the IL-1 family member IL-33 in lung defense against A. fumigatus. IL-33 was detected in the naive lung, which further increased after exposure to A. fumigatus in a dectin-1\u2013independent manner. Mice deficient in the receptor for IL-33 (Il1rl1\u2212\/\u2212) unexpectedly demonstrated enhanced lung clearance of A. fumigatus. IL-33 functioned as a negative regulator of multiple inflammatory cytokines, as IL-1\u03b1, IL-1\u03b2, IL-6, IL-17A, and IL-22 were significantly elevated in fungal-exposed Il1rl1\u2212\/\u2212 mice. Subsequently, IL-33 administration to normal mice attenuated fungal-induced IL-17A and IL-22, but not IL-1\u03b1, IL-1\u03b2, or IL-6, production. IL-33\u2013mediated regulation of IL-17A and IL-22 did not involve the modulation of IL-23 but rather PGE2; PGE2 was significantly increased in fungal-exposed Il1rl1\u2212\/\u2212 mice, and normal mice produced less PGE2 after fungal exposure when administered IL-33, suggesting that IL-33\u2013mediated regulation of IL-17A and IL-22 occurred at the level of PGE2. This was confirmed by in vivo cyclooxygenase 2 inhibition, which attenuated fungal-induced IL-17A and IL-22, as well as IL-1\u03b1, IL-1\u03b2, and IL-6, production in Il1rl1\u2212\/\u2212 mice, resulting in impaired fungal clearance. We also show that a PGE2 receptor agonist increased, whereas a PGE2 synthase inhibitor decreased, the levels of IL-17A and IL-22 but not IL-1\u03b1, IL-1\u03b2, or IL-6. This study establishes novel mechanisms of innate IL-17A\/IL-22 production via PGE2 and regulation of the PGE2\/IL-17A\/IL-22 axis via IL-33 signaling during lung fungal exposure.<\/jats:p>","DOI":"10.4049\/jimmunol.1602186","type":"journal-article","created":{"date-parts":[[2017,8,8]],"date-time":"2017-08-08T00:30:25Z","timestamp":1502152225000},"page":"2140-2148","source":"Crossref","is-referenced-by-count":39,"title":["IL-33 Signaling Regulates Innate IL-17A and IL-22 Production via Suppression of Prostaglandin E2 during Lung Fungal Infection"],"prefix":"10.1093","volume":"199","author":[{"given":"Jaleesa M","family":"Garth","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Alabama at Birmingham , Birmingham, AL 35294"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen M","family":"Reeder","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alabama at Birmingham , Birmingham, AL 35294"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew S","family":"Godwin","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alabama at Birmingham , Birmingham, AL 35294"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph J","family":"Mackel","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alabama at Birmingham , Birmingham, AL 35294"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad W","family":"Dunaway","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alabama at Birmingham , Birmingham, AL 35294"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan P","family":"Blackburn","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alabama at Birmingham , Birmingham, AL 35294"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad","family":"Steele","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alabama at Birmingham , Birmingham, AL 35294"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,9,15]]},"reference":[{"key":"2025030614304745200_r1","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1126\/science.1222236","article-title":"Tackling human fungal infections","volume":"336","author":"Brown","year":"2012","journal-title":"Science"},{"key":"2025030614304745200_r2","doi-asserted-by":"crossref","first-page":"538","DOI":"10.3109\/13693786.2011.630040","article-title":"Impact of the revised (2008) EORTC\/MSG definitions for invasive fungal disease on the rates of diagnosis of invasive aspergillosis","volume":"50","author":"Tsitsikas","year":"2012","journal-title":"Med. 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