{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:48:54Z","timestamp":1790794134319,"version":"4.1.0"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2016,2,1]],"date-time":"2016-02-01T00:00:00Z","timestamp":1454284800000},"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":[[2016,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>IL-13 and IL-17A, produced mainly by Th2 and Th17 cells, respectively, have an influential role in asthma pathogenesis. We examined the role of IL-13 and IL-17A in mediating airway hyperresponsiveness (AHR), lung inflammation, and mucus metaplasia in a dual Th2\/Th17 model of asthma. IL-13 and\/or IL-17A were neutralized using mAbs. Th2\/Th17 adoptive transfer induced a mixed asthma phenotype characterized by elevated eosinophilia and neutrophilia, tissue inflammation, mucus metaplasia, and AHR that were partially reversible with steroid treatment. Pulmonary inflammation and quasi-static lung compliance were largely unaffected by neutralization of IL-13 and\/or IL-17A. However, neutralization of IL-13 alone or in combination with IL-17A significantly attenuated AHR and mucus metaplasia. Further, STAT6 activation was attenuated following IL-13 and IL-13\/IL-17A Ab treatment. We next assessed the role of STAT6 in Th2\/Th17-mediated allergic airway disease using STAT6\u2212\/\u2212 mice. STAT6\u2212\/\u2212 mice adoptively transferred with Th2\/Th17 cells had decreased AHR compared with controls. These data suggest that IL-13 drives AHR and mucus metaplasia in a STAT6-dependent manner, without directly contributing to airway or tissue inflammation. IL-17A independently contributes to AHR, but it only partially mediates inflammation and mucus metaplasia in a mixed Th2\/Th17 model of steroid-resistant asthma.<\/jats:p>","DOI":"10.4049\/jimmunol.1501531","type":"journal-article","created":{"date-parts":[[2016,1,5]],"date-time":"2016-01-05T01:49:04Z","timestamp":1451958544000},"page":"963-977","source":"Crossref","is-referenced-by-count":47,"title":["Molecular Mechanisms of Airway Hyperresponsiveness in a Murine Model of Steroid-Resistant Airway Inflammation"],"prefix":"10.1093","volume":"196","author":[{"given":"Michelle L","family":"Manni","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital of Pittsburgh of University of Pittsburgh Medical Center , Pittsburgh, PA 15224"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sivanarayana","family":"Mandalapu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital of Pittsburgh of University of Pittsburgh Medical Center , Pittsburgh, PA 15224"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin J","family":"McHugh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital of Pittsburgh of University of Pittsburgh Medical Center , Pittsburgh, PA 15224"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M Merle","family":"Elloso","sequence":"additional","affiliation":[{"name":"Janssen Research & Development, LLC , Spring House, PA 19477"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul L","family":"Dudas","sequence":"additional","affiliation":[{"name":"Janssen Research & Development, LLC , Spring House, PA 19477"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John F","family":"Alcorn","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital of Pittsburgh of University of Pittsburgh Medical Center , Pittsburgh, PA 15224"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,2,1]]},"reference":[{"key":"2025030702122560300_r1","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1111\/j.1365-2222.2011.03929.x","article-title":"Severe asthma: from characteristics to phenotypes to endotypes","volume":"42","author":"Wenzel","year":"2012","journal-title":"Clin. 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