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Foxa2 is required for normal airway epithelial differentiation, and its deletion causes goblet-cell metaplasia and Th2-mediated pulmonary inflammation during postnatal development. Foxa2 expression is inhibited during aeroallergen sensitization and after stimulation with Th2 cytokines, when its loss is associated with goblet-cell metaplasia. Mechanisms by which Foxa2 controls airway epithelial differentiation and Th2 immunity are incompletely known. During the first 2 weeks after birth, the loss of Foxa2 increases the production of leukotrienes (LTs) and Th2 cytokines in the lungs of Foxa2 gene\u2013targeted mice. Foxa2 expression inhibited 15-lipoxygenase (Alox15) and increased Alox5 transcription, each encoding key lipoxygenases associated with asthma. The inhibition of the cysteinyl LT (CysLT) signaling pathway by montelukast inhibited IL-4, IL-5, eotaxin-2, and regulated upon activation normal T cell expressed and presumably secreted expression in the developing lungs of Foxa2 gene\u2013targeted mice. Montelukast inhibited the expression of genes regulating mucus metaplasia, including Spdef, Muc5ac, Foxa3, and Arg2. Foxa2 plays a cell-autonomous role in the respiratory epithelium, and is required for the suppression of Th2 immunity and mucus metaplasia in the developing lung in a process determined in part by its regulation of the CysLT pathway.<\/jats:p>","DOI":"10.1165\/rcmb.2013-0122oc","type":"journal-article","created":{"date-parts":[[2013,7,3]],"date-time":"2013-07-03T16:37:29Z","timestamp":1372869449000},"page":"960-970","source":"Crossref","is-referenced-by-count":29,"title":["Foxa2 Regulates Leukotrienes to Inhibit Th2-mediated Pulmonary Inflammation"],"prefix":"10.1093","volume":"49","author":[{"given":"Xiaoju","family":"Tang","sequence":"first","affiliation":[{"name":"Research Center of Regeneration Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojing J.","family":"Liu","sequence":"additional","affiliation":[{"name":"Laboratory of 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