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It is characterized by infiltration of diverse inflammatory cells and thickening of pulmonary septum along with oxidative stress to airway epithelial cells. STAT6 is a nuclear transcription factor that plays a crucial role in orchestrating the immune response, but its function in tissue inflammatory injury has not been comprehensively studied. Here, we demonstrated that STAT6 activation can protect against particle\u2010induced lung inflammatory injury by resisting oxidative stress. Specifically, genetic ablation of STAT6 was observed to worsen particle\u2010induced lung injury mainly by disrupting the lungs\u2019 antioxidant capacity, as reflected by the downregulation of the Nrf2 signaling pathway, an increase in malondialdehyde levels, and a decrease in glutathione levels. Vitamin D receptor (VDR) has been previously proved to positively regulate Nrf2 signals. In this study, silencing VDR expression in human bronchial epithelial BEAS\u20102B cells consistently suppressed autophagy\u2010mediated activation of the Nrf2 signaling pathway, thereby aggravating particle\u2010induced cell damage. Mechanically, STAT6 activation promoted the nuclear translocation of VDR, which increased the transcription of autophagy\u2010related genes and induced Nrf2 signals, and silencing VDR abolished these effects. Our research provides important insights into the role of STAT6 in oxidative damage and reveals its potential underlying mechanism. This information not only deepens the appreciation of STAT6 but also opens new avenues for the discovery of therapies for inflammatory respiratory system disorders.<\/jats:p>","DOI":"10.1155\/2022\/2485250","type":"journal-article","created":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T20:50:08Z","timestamp":1641847808000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["STAT6\/VDR Axis Mitigates Lung Inflammatory Injury by Promoting Nrf2 Signaling Pathway"],"prefix":"10.1155","volume":"2022","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1517-6119","authenticated-orcid":false,"given":"Youjing","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3216-1119","authenticated-orcid":false,"given":"Qianmin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8765-9005","authenticated-orcid":false,"given":"Shuhui","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9039-6605","authenticated-orcid":false,"given":"Kaimiao","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9493-8291","authenticated-orcid":false,"given":"Lian","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8782-1615","authenticated-orcid":false,"given":"Jie","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2175-3346","authenticated-orcid":false,"given":"Yu","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6765-3829","authenticated-orcid":false,"given":"Shasha","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,1,10]]},"reference":[{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00924"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/celldisc.2017.9"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.05.004"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12989-020-00353-3"},{"key":"e_1_2_10_5_2","article-title":"Airborne particulate matter induces oxidative damage, DNA adduct formation and alterations in DNA repair pathways","volume":"2021","author":"Quezada-Maldonado E. 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