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Signal transducer and activator of transcription 3 (STAT3) induce both suppressors of cytokine signaling 3 (SOCS3) and retinoic acid receptor\u2010related orphan nuclear receptor \u03b3 (ROR\u03b3t) to initiate Th17 cell differentiation which is inhibited by SOCS3, a negative feedback regulator of STAT3. Heme oxygenase\u20101 (HO\u20101) is a stress\u2010responsive, cytoprotective, and immunoregulatory molecular. Two other isoforms of the enzyme includes HO\u20102 and HO\u20103. Because HO\u20102 does not exhibit stress\u2010related upregulation and distributes mainly in nervous system and HO\u20103 shows a low enzymatic activity, we tested a hypothesized anti\u2010inflammatory role for HO\u20101 in EA by inhibiting STAT3\u2010SOCS3 signaling. Animal model was established with Ovalbumin in wild type Balb\/C mice. Hemin or SNPP was intraperitoneally (IP) injected ahead of the animal model to induce or inhibit HO\u20101 expression. Airway inflammation was evaluated by bronchoalveolar lavage, hematoxyline and eosin staining, enzyme\u2010linked immunosorbent assay, and Western blot analysis. In vivo results showed that HO\u20101 induction inhibited phosphorylation of STAT3 and expression of SOCS3 and ROR\u03b3t, decreased Th2 and Th17 immune responses, and alleviated airway inflammation. In vitro results revealed that HO\u20101 inhibited phosphorylation of STAT3 and expression of SOCS3 in naive CD4<jats:sup>+<\/jats:sup> T cells. These findings identify HO\u20101 induction as a potential therapeutic strategy for EA treatment by reducing STAT3 phosphorylation, STAT3\u2010SOCS3\u2010mediated Th2\/Th17 immune responses, and ultimate allergic airway inflammation.<\/jats:p>","DOI":"10.1002\/ppul.24759","type":"journal-article","created":{"date-parts":[[2020,4,16]],"date-time":"2020-04-16T11:35:03Z","timestamp":1587036903000},"page":"1440-1447","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Heme oxygenase\u20101 alleviates eosinophilic inflammation by inhibiting STAT3\u2010SOCS3 signaling"],"prefix":"10.1002","volume":"55","author":[{"given":"Xiaoliang","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Pediatrics the First Affiliated Hospital of Xiamen University  Xiamen 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