Abstract: Interleukin-33 (IL-33) is released in response to cellular damage and mediates its biological effects by binding to its specific receptor, growth stimulation expressed gene 2 (ST2), thereby activating both innate and adaptive immune responses. Accumulating evidence indicates that the ST2/IL-33 signaling pathway plays a critical role in the initiation and progression of chronic airway inflammatory diseases, including chronic obstructive pulmonary disease (COPD) and asthma, and has emerged as a major focus of current research. However, the available findings have not yet been systematically integrated. This review comprehensively summarized the physiological functions and pathological mechanisms of the ST2/IL-33 pathway. And it further highlighted recent advances in clinical studies of biologics targeting this axis, such as anti-IL-33 and anti-ST2 monoclonal antibodies, in COPD and asthma. Current data indicated that activation of the ST2/IL-33 pathway contributes to airway inflammation, mucus hypersecretion, airway remodeling, and acute exacerbations through immune-mediated mechanisms. Correspondingly, emerging clinical trial data demonstrated that biologics targeting this pathway could improve lung function and reduce the frequency of acute exacerbations. In summary, the ST2/IL-33 pathway represents a central inflammatory regulatory mechanism in chronic airway diseases and provides a promising therapeutic target. As the high-quality clinical evidence continues to accumulate, targeting the ST2/IL-33 pathway may offer a novel strategy for the treatment of chronic airway diseases, with the potential to improve long-term outcomes and quality of life for patients.

Key words: Chronic airway diseases, ST2, IL-33, Signaling pathway, Mechanism of action

摘要： 白介素33（IL-33）在细胞损伤时释放，并通过与受体生长刺激表达基因2蛋白（ST2）受体结合，激活先天和适应性免疫反应。ST2/IL-33通路在慢性阻塞性肺疾病、哮喘等慢性气道疾病的炎症发生和发展中发挥重要作用，并成为了研究的热点，但现有研究成果尚缺少系统总结。本文系统综述了ST2/IL-33通路的生理功能和病理机制，并总结了靶向ST2/IL-33的生物制剂在慢性阻塞性肺疾病和哮喘的临床研究进展。研究表明ST2/IL-33通路通过激活免疫反应，在驱动气道炎症、黏液高分泌、组织重塑和急性加重中发挥关键作用，靶向其通路的生物制剂可改善患者的肺功能，并降低急性加重风险。总之，ST2/IL-33通路不仅可作为慢性气道疾病的炎症调控机制，也为开发新型靶向治疗提供了方向。随着更多临床证据的出现，靶向ST2/IL-33通路有望成为治疗慢性气道疾病的新方法，从而改善患者的长期预后和生活质量。

关键词: 慢性气道疾病, ST2, IL-33, 信号通路, 作用机制