{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T19:02:10Z","timestamp":1791140530924,"version":"4.1.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2009,2,1]],"date-time":"2009-02-01T00:00:00Z","timestamp":1233446400000},"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":[[2009,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>IL-25 initiates, promotes, and augments Th2 immune responses. In this study, we report that Act1, a key component in IL-17-mediated signaling, is an essential signaling molecule for IL-25 signaling. Although Act1-deficient mice showed reduced expression of KC (CXCL1) and neutrophil recruitment to the airway compared with wild-type mice in response to IL-17 stimulation, Act1 deficiency abolished IL-25-induced expression of IL-4, IL-5, IL-13, eotaxin-1 (CCL11), and pulmonary eosinophilia. Using a mouse model of allergic pulmonary inflammation, we observed diminished Th2 responses and lung inflammation in Act1-deficient mice compared with wild-type mice. Importantly, Act1 deficiency in epithelial cells reduced the phenotype of allergic pulmonary inflammation due to loss of IL-17-induced neutrophilia and IL-25-induced eosinophilia, respectively. These results demonstrate the essential role of epithelial-derived Act1 in allergic pulmonary inflammation through the distinct impact of the IL-17R-Act1 and IL-25R-Act1 axes. Such findings are crucial for the understanding of pathobiology of atopic diseases, including allergic asthma, which identifies Act1 as a potential therapeutic target.<\/jats:p>","DOI":"10.4049\/jimmunol.182.3.1631","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:01:40Z","timestamp":1397847700000},"page":"1631-1640","source":"Crossref","is-referenced-by-count":124,"title":["The Critical Role of Epithelial-Derived Act1 in IL-17- and IL-25-Mediated Pulmonary Inflammation"],"prefix":"10.1093","volume":"182","author":[{"given":"Shadi","family":"Swaidani","sequence":"first","affiliation":[{"name":"Department of Immunology"},{"name":"Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University , Cleveland, OH 44195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Bulek","sequence":"additional","affiliation":[{"name":"Department of Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zizhen","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caini","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiguo","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Aronica","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, Cleveland Clinic Foundation , Cleveland, OH 44195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxia","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,2,1]]},"reference":[{"key":"2026012806213874000_R1","first-page":"405","article-title":"To respond or not to respond: T cells in allergic asthma.","volume-title":"Nat. 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