Airway epithelial integrin β4 suppresses allergic inflammation by decreasing CCL17 production.

Abstract

Airway epithelial cells (AECs) play a key role in asthma susceptibility and severity. Integrin β4 (ITGB4) is a structural adhesion molecule that is down-regulated in the airway epithelium of asthma patients. Although a few studies hint toward the role of ITGB4 in asthmatic inflammation pathogenesis, their specific resultant effects remain unexplored. In the present study, we determined the role of ITGB4 of AECs in the regulation of Th2 response and identified the underpinning molecular mechanisms. We found that ITGB4 deficiency led to exaggerated lung inflammation and AHR with higher production of CCL17 in house dust mite (HDM)-treated mice. ITGB4 regulated CCL17 production in AECs through EGFR, ERK and NF-κB pathways. EFGR-antagonist treatment or the neutralization of CCL17 both inhibited exaggerated pathological marks in HDM-challenged ITGB4-deficient mice. Together, these results demonstrated the involvement of ITGB4 deficiency in the development of Th2 responses of allergic asthma by down-regulation of EGFR and CCL17 pathway in AECs.

• Authors: Lin Yuan, Xun Zhang, Ming Yang, Xizi Du, Leyuan Wang, Shuangyan Wu, Mengping Wu, Zhen Duan, Gelei Xiao, Yizhou Zou, Yang Xiang, Xiangping Qu, Huijun Liu, Ling Qin, Qingwu Qin, Xiaoqun Qin, Chi Liu
• Journal: Clinical science (London, England : 1979) (Clin Sci (Lond)) Vol. 134 Issue 13 Pg. 1735-1749 (07 17 2020) ISSN: 1470-8736 [Electronic] England
• PMID: 32608482 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Chemical References

• Ccl17 protein, mouse
• Chemokine CCL17
• Integrin beta4
• Itgb4 protein, mouse
• EGFR protein, mouse
• ErbB Receptors

Topics

• Animals
• Asthma (genetics, immunology)
• Chemokine CCL17 (genetics, immunology)
• Epithelial Cells (immunology)
• ErbB Receptors (genetics, immunology)
• Female
• Humans
• Integrin beta4 (genetics, immunology)
• Lung (immunology)
• Male
• Mice
• Mice, Knockout
• Th2 Cells (immunology)