IL-17A is elevated in patients with COPD and contributes to airway remodeling by acting on fibroblasts

Abstract

Background: Airway wall thickening is the major cause of decreased lung function in chronic obstructive pulmonary disease (COPD). Recent studies suggest that interleukin (IL)-17A has been implicated in the pathogenesis of COPD.However, its role in airway remodeling in COPD has not beenfully elucidated. Aims and objectives: We aimed to determine whether IL-17A plays a functional role in airway remodeling of COPD, and the possible underlying mechanisms. Methods: We examined the expression of IL-17A in small airways from smokers with COPD and controls by immunohistochemistry, and then the association between IL-17A expression and airway remodeling was analyzed. In parallel, IL-17Adeficiency (IL-17A -/- ) mice and wild-type (WT) mice were exposed to cigarette smoke (CS) or room air for 3 months, and the airway inflammation and remodeling were assessed. In vitro , primary human lung fibroblasts were exposed to IL-17A, and the proliferation and collagen synthesis of fibroblasts were evaluated. Results: IL-17A immunoreactivity was significantly elevated in smokers with COPD compared with controls, andwas positively correlated with collagen deposition. CS-exposed IL-17A -/- mice exhibited reduced airway inflammation, smooth muscle area, and lung collagen content as compared with WT mice. IL-17A induced proliferation and collagen synthesis of human primary lung fibroblasts, which was TGF-β1 mediated. Conclusions: IL-17A is critical for the development of airway remodeling in CS-induced COPD. Targeting IL-17A inhibition may thus be beneficial to attenuate airway remodeling in COPD by suppressing airway inflammation and decreasing lung fibroblast activation.