AUTHOR=Du Xizi , Yuan Lin , Yao Ye , Yang Yu , Zhou Kai , Wu Xinyu , Wang Leyuan , Qin Ling , Li Wenkai , Xiang Yang , Qu Xiangping , Liu Huijun , Qin Xiaoqun , Yang Ming , Liu Chi 

TITLE=ITGB4 Deficiency in Airway Epithelium Aggravates RSV Infection and Increases HDM Sensitivity

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.912095

DOI=10.3389/fimmu.2022.912095

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>The heterogeneity of RSV-infected pathology phenotype in early life is strongly associate with increased susceptibility of asthma in later life. However, the inner mechanism of this heterogeneity is still obscure. ITGB4 is a down-regulated adhesion molecular in the airway epithelia of asthma patients which may participate in the regulation of RSV infection related intracellular pathways.</p></sec><sec><title>Object</title><p>This study was designed to observe the involvement of ITGB4 in the process of RSV infection and the effect of ITGB4 deficiency on anti-RSV responses of airway epithelia.</p></sec><sec><title>Results</title><p>RSV infection caused a transient decrease of ITGB4 expression both <italic>in vitro</italic> and <italic>in vivo</italic>. Besides, ITGB4 deficiency induced not only exacerbated RSV infection, but also enhanced HDM sensitivity in later life. Moreover, IFN III (IFN-λ) was significantly suppressed during RSV infection in ITGB4 deficient airway epithelial cells. Furthermore, the suppression of IFN-λ were regulated by IRF-1 through the phosphorylation of EGFR in airway epithelial cells after RSV infection.</p></sec><sec><title>Conclusion</title><p>These results demonstrated the involvement of ITGB4 deficiency in the development of enhance RSV infection in early life and the increased HDM sensitivity in later life by down-regulation of IFN-λ through EGFR/IRF-1 pathway in airway epithelial cells.</p></sec>