Cheng Fuying, Wang Yizhang, Gao Yingqi, Zhang Chen, Zhang Qianqian, Chen Jiani, Zhou Yumin, Shi Le, Hu Li, Wang Huan, Zhang Yaguang, Sun Xicai
High Altitude Rhinology Research Center, Eye & ENT Hospital of Fudan University and People's Hospital of Shigatse City, Shanghai, Shigatse, China.
ENT Institute and Department of Otorhinolaryngology, Eye and ENT Hospital, Fudan University, Shanghai, 200031, China.
Clin Rev Allergy Immunol. 2025 Jun 18;68(1):59. doi: 10.1007/s12016-025-09073-y.
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.
伴鼻息肉的慢性鼻-鼻窦炎（CRSwNP）是一种多因素炎症性疾病，其特征为鼻窦持续炎症和组织重塑。上皮来源的警报素，包括胸腺基质淋巴细胞生成素（TSLP）、白细胞介素-33（IL-33）和白细胞介素-25（IL-25），是启动和放大CRSwNP免疫反应的关键介质。这些警报素由应激或受损的鼻上皮细胞分泌，以应对环境刺激，如过敏原、微生物感染、污染物和蛋白酶。一旦释放，它们会协调免疫细胞激活并放大炎症途径。靶向上皮来源的警报素已成为CRSwNP一种有前景的治疗策略，包括TSLP和IL-33抑制剂在内的几种生物制剂显示出令人鼓舞的临床结果。本综述重点关注上皮来源的警报素在CRSwNP中的作用，研究它们的表达模式、调节机制及其对炎症的贡献，评估警报素靶向治疗的当前进展，并探索优化其临床应用的未来研究方向。
