IL-17A activates the PI3K/AKT/mTOR pathway to regulate bronchial fibroblast autophagy-mediated airway remodeling: evidence from conditional IL-17RA-deficient mice

作者：Yuting Liu, J Zhou, Xuan An, Yanhui Gu, Li Zhang, Yue Ma, Qingpiao Tang, Shengyi Yu, Yao Ouyang · 发表于：Frontiers in Physiology · 年份：2026 · DOI：10.3389/fphys.2026.1873777 · 研究领域：Autophagy in Disease and Therapy、Asthma and respiratory diseases、Chronic Obstructive Pulmonary Disease (COPD) Research

Background: Airway remodeling (AR) is a key pathological feature of chronic lung diseases and is closely associated with disease progression. IL-17A has been implicated in airway inflammation and fibrosis, but its role in AR and the underlying mechanisms remain incompletely understood. This study investigated whether IL-17A regulates bronchial fibroblast autophagy and airway remodeling through the PI3K/AKT/mTOR pathway. Methods: An AR mouse model was established by intratracheal administration of an adenovirus expressing IL-1β. Lung histopathology and pulmonary function were evaluated in wild-type mice and conditional IL-17RA-deficient mice. Primary mouse bronchial fibroblasts were used to assess the effects of IL-17A on autophagy-related proteins, inflammatory and profibrotic mediator secretion, collagen production, and PI3K/AKT/mTOR pathway activation. The autophagy inhibitor 3-methyladenine (3MA) was used to further examine the relationship between autophagy and pathway activation. Results: Conditional IL-17RA deficiency attenuated airway inflammation, collagen deposition, and pulmonary function impairment in AR mice. In primary bronchial fibroblasts, IL-17A decreased LC3II/I expression, increased p62 expression, promoted collagen I/III production, altered inflammatory and profibrotic mediator secretion, and activated the PI3K/AKT/mTOR pathway. These effects were reduced in fibroblasts with lower IL-17RA expression. Moreover, IL-17A partially reversed the inhibitory effect...