Role of endothelial Sox17 in allergic airway inflammation

Abstract

Asthma is a heterogeneous disease with chronic inflammation and remodeling of airway. Sox17 is regarded as a transcription factor of vascular network regulating various pro-angiogenic target genes. Recently, IL-33, a critical cytokine linking to recruitment and activation of ILC2 prior to Th2 immune responses, was reported induce up-regulation of Sox17 transcription. However, the role of Sox17 related with IL-33 in the development of allergic airway inflammation was not clearly evaluated. We established conventional mouse model of asthma in WT and Sox17 endothelial conditional knock-out mice, and evaluated airway inflammation in BAL fluid and lung tissues. We sorted endothelial cells from these mice and evaluated various chemical mediators by qRT-PCR. To investigate underlying mechanism in endothelial cells, Sox17 was silenced or over-expressed in IL-33 activated HUVECs and HPMECs then evaluated various cytokines and chemokines. In the airway of asthmatic mice, Sox17 expression was significantly enhanced, and absence of Sox17 was resulted in down-regulation of Th2 airway inflammation. Among inflammatory cells, inflammatory dendritic cells and monocytes were decreased, and these were accompanied by down-regulation of cytokines and adhesion molecules in sorted endothelial cells from lung tissues. IL-33 stimulated endothelial cells showed positive correlation between Sox17 expression and chemokine secretion after knock-down or over-expression of Sox17. These results demonstrated that Sox17 is involved with the development of allergic airway inflammation through IL-33 associated activation of endothelial cells.