Targeting STING to attenuate autophagy-mediated airway remodeling in asthma

Stimulator of interferon genes (STING) is critical for antiviral and intracellular antibacterial immune defense and is involved in pulmonary fibrotic diseases. However, the role of STING in regulating autophagy and airway remodeling in asthma remains unclear. An ovalbumin (OVA)-induced mouse model of asthma airway remodeling was established. Expression levels of STING and autophagy-related gene 5 (ATG5) in lung tissues were detected. The effects of STING inhibitor C-176 on autophagy and airway remodeling were evaluated in vivo. In human bronchial epithelial BEAS-2B cells stimulated with interleukin (IL)-13, the relationships among STING, autophagy, and cellular fibrosis were investigated in vitro. In OVA-challenged mice, C-176, chloroquine (CQ), and dexamethasone (DX) reduced airway hyperresponsiveness and eosinophil counts. C-176 and CQ alleviated inflammatory cell infiltration, mucus secretion, and collagen deposition, and suppressed autophagy and fibrosis in airway epithelium. In IL-13-stimulated BEAS-2B cells, C-176, ATG5 inhibition, or PERK pathway inhibition downregulated autophagy and fibrosis‑related markers. STING upregulation in airway epithelial cells promotes autophagy and subsequent airway remodeling in asthma. Inhibition of STING or autophagy attenuates these pathological changes, indicating a potential therapeutic target for asthma.