alexa The overexpression of heparin-binding epidermal growth factor is responsible for Th17-induced airway remodeling in an experimental asthma model.


Journal of Allergy & Therapy

Author(s): Wang Q, Li H, Yao Y, Xia D, Zhou J

Abstract Share this page

Abstract Th17 cells that produce IL-17 have been found to participate in the development of allergy-triggered asthma. However, whether they play a causative role in the pathogenesis of airway remodeling in chronic asthma remains unclear. In this study, we investigated the role of Th17 cells in airway remodeling and the possible involvement of epidermal growth factor (EGF) receptor signals downstream of Th17. We established a C57BL/6 mouse model of prolonged allergen challenge that exhibits many characteristics of airway remodeling. Prolonged allergen challenge induced a progressive increase in the number of airway-infiltrating Th17 cells, and Th17 counts positively correlated with the severity of airway remodeling. Increases in mucus production, airway smooth muscle (ASM) mass, peribronchial collagen deposition, and airway heparin-binding EGF (HB-EGF) expression have been observed in sensitized mice following prolonged allergen exposure or adoptive Th17 transfer; remarkably, these effects can be abrogated by treatment with anti-IL-17 mAb. Both the EFGR inhibitor AG1478 and an anti-HB-EGF mAb ameliorated all of these effects, except for peribronchial collagen deposition in the presence of high levels of IL-17. In vitro, Th17 cells enhanced the airway epithelial expression of HB-EGF in a coculture of the two cells. The conditioned medium obtained from this coculture system effectively promoted ASM proliferation; this response was dramatically abolished by anti-HB-EGF mAb but not Abs against other EGF receptor ligands or IL-17. These observations demonstrated that overexpression of airway HB-EGF induced by IL-17 secreted from redundant expanding Th17 cells might contribute to excessive mucus expression and ASM proliferation in chronic asthma. This article was published in J Immunol and referenced in Journal of Allergy & Therapy

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Relevant Topics

Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version