PT  - JOURNAL ARTICLE
AU  - Lin Yuan
AU  - Xun Zhang
AU  - Ming Yang
AU  - Yizhou Zou
AU  - Yang Xiang
AU  - Xiangping Qu
AU  - Huijun Liu
AU  - Xizi Du
AU  - Leyuan Wang
AU  - Shuangyan Wu
AU  - Mengping Wu
AU  - Ling Qin
AU  - Qingwu Qin
AU  - Xiaoqun Qin
AU  - Chi Liu
TI  - Airway epithelial integrin β4 suppresses allergic inflammation by decreasing CCL17 production
AID  - 10.1101/513499
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 513499
4099  - http://biorxiv.org/content/early/2019/01/07/513499.short
4100  - http://biorxiv.org/content/early/2019/01/07/513499.full
AB  - Airway epithelial cells (AECs) play a key role in asthma susceptibility and severity. Integrin β4 (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-κB 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.