Current Understanding of Epithelial-Derived Alarmins in Chronic Rhinosinusitis with Nasal Polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory condition characterized by persistent sinus inflammation and tissue remodeling. Epithelial-derived alarmins, including thymic stromal lymphopoietin (TSLP), interleukin-33 (IL-33), and interleukin-25 (IL-25), are critical mediators that initiate and amplify immune responses in CRSwNP. These alarmins are secreted by stressed or damaged nasal epithelial cells in response to environmental insults, such as allergens, microbial infections, pollutants, and proteases. Once released, they orchestrate immune cell activation and amplify inflammatory pathways. Targeting epithelial-derived alarmins has emerged as a promising therapeutic strategy for CRSwNP, with several biologics, including TSLP and IL-33 inhibitors, showing encouraging clinical outcomes. This review focuses on the role of epithelial-derived alarmins in CRSwNP, examining their expression patterns, regulatory mechanisms, and contributions to inflammation, evaluating the current progress in alarmin-targeted therapies, and exploring future research directions to optimize their clinical application.