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However, the deficiency of IRF<\/jats:styled-content>7 increases the susceptibility to deadly IAV<\/jats:styled-content> infection in both humans and mice. To test whether the attenuation rather than the abolishment of IRF<\/jats:styled-content>7 activity in local infectious sites could alleviate IAV<\/jats:styled-content>\u2010induced ALI<\/jats:styled-content>, we established IAV<\/jats:styled-content>\u2010infected mouse model and trachea\/lung\u2010tissue culture systems, and designed two IRF<\/jats:styled-content>7\u2010interfering oligodeoxynucleotides, IRF<\/jats:styled-content>7\u2010rODN<\/jats:styled-content> M1 and IRF<\/jats:styled-content>7\u2010rODN<\/jats:styled-content> A1, based on the mouse and human consensus sequences of IRF<\/jats:styled-content>7\u2010binding sites of Ifna<\/jats:italic>\/IFNA<\/jats:styled-content><\/jats:italic> genes, respectively. In the model mice, we found a close relationship between the IAV<\/jats:styled-content>\u2010induced ALI<\/jats:styled-content> and the level\/activity of IRF<\/jats:styled-content>7 in local infectious sites, and also found that the reduced IRF<\/jats:styled-content>7 level or activity in the lungs of mice treated with IRF<\/jats:styled-content>7\u2010rODN<\/jats:styled-content> M1 led to decreased mRNA<\/jats:styled-content> levels of Ifna<\/jats:italic> genes, reduced neutrophil infiltration in the lungs and prolonged survival of mice. Furthermore, we found that the effects of IRF<\/jats:styled-content>7\u2010rODN<\/jats:styled-content> M1 on alleviating IAV<\/jats:styled-content>\u2010induced ALI<\/jats:styled-content> could be correlated to the reduced translocation of IRF<\/jats:styled-content>7, caused by the IRF<\/jats:styled-content>7\u2010rODN<\/jats:styled-content> M1, from cytosol to nucleus in IAV<\/jats:styled-content>\u2010infected cells. These data suggest that the proper attenuation of IRF<\/jats:styled-content>7 activity in local infectious sites could be a novel approach for treating IAV<\/jats:styled-content>\u2010induced ALI.<\/jats:p>","DOI":"10.1111\/imm.13045","type":"journal-article","created":{"date-parts":[[2019,1,23]],"date-time":"2019-01-23T22:00:02Z","timestamp":1548280802000},"page":"37-51","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Attenuation of interferon regulatory factor 7 activity in local infectious sites of trachea and lung for preventing the development of acute lung injury caused by influenza A virus"],"prefix":"10.1111","volume":"157","author":[{"given":"Lei","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Molecular Biology in College of Basic Medical Sciences and Institute of Pediatrics in The First Hospital of Jilin University Jilin University Changchun Jilin 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