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bioRxiv · 10.1101/513499

Airway epithelial integrin β4 suppresses allergic inflammation by decreasing CCL17 production

Chi, L.·Yuan, L.·Zhang, X.·Yang, M.·Zou, Y.·Xiang, Y.·Qu, X.·Liu, H.·Du, X.·Wang, L.·Wu, S.·Wu, M.·Qin, L.·Qin, Q.·Qin, X.
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Abstract

Airway epithelial cells (AECs) play a key role in asthma susceptibility and severity. Integrin {beta}4 (ITGB4) is a structural adhesion molecule that is downregulated in the airway epithelium of asthma patients. Specific ITGB4 deficiency in AECs induces exaggerated Th2 responses, severe allergen-induced airway inflammation and airway hyperresponsiveness (AHR) in mouse model of allergic asthma. However, the underlying mechanisms remain unexplored. In this study, we determine the role of ITGB4 of AECs in the regulation of Th2 response and in the induction of asthma and identify the underpinning molecular mechanisms. We found that ITGB4 deficiency led to exaggerated Th2 cells infiltration, inflammation and AHR and higher production of CCL17 in HDM treated mice. ITGB4-regulated CCL17 production in AECs was regulated by EGFR, ERK and NF-{kappa}B pathways. EFGR-antagonist treatment or the neutralization of CCL17 by antibody inhibited exaggerated pathological marks in HDM-challenged ITGB4-deficient mice. Together, these results demonstrated that ITGB4 of AECs negatively regulates the development of Th2 responses of allergic asthma by down-regulation of EGFR and CCL17 pathway.

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Chi, L., Yuan, L., Zhang, X., Yang, M., Zou, Y., Xiang, Y., Qu, X., Liu, H., Du, X., Wang, L., Wu, S., Wu, M., Qin, L., Qin, Q., Qin, X.. 2019-01-07. Airway epithelial integrin β4 suppresses allergic inflammation by decreasing CCL17 production. https://doi.org/10.1101/513499

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