Hansi Ravneet K, Ranjbar Maral, Whetstone Christiane E, Gauvreau Gail M
Division of Respirology, Department of Medicine, McMaster University, Hamilton, ON L8N 3Z5, Canada.
Biomedicines. 2024 Oct 11;12(10):2312. doi: 10.3390/biomedicines12102312.
Asthma is a chronic respiratory condition predominantly driven by a type 2 immune response. Epithelial-derived alarmins such as thymic stromal lymphopoietin (TSLP), interleukin (IL)-33, and IL-25 orchestrate the activation of downstream Th2 cells and group 2 innate lymphoid cells (ILC2s), along with other immune effector cells. While these alarmins are produced in response to inhaled triggers, such as allergens, respiratory pathogens or particulate matter, disproportionate alarmin production by airway epithelial cells can lead to asthma exacerbations. With alarmins produced upstream of the type 2 inflammatory cascade, understanding the pathways by which these alarmins are regulated and expressed is critical to further explore new therapeutics for the treatment of asthmatic patients. This review emphasizes the critical role of airway epithelium and epithelial-derived alarmins in asthma pathogenesis and highlights the potential of targeting alarmins as a promising therapeutic to improve outcomes for asthma patients.
哮喘是一种主要由2型免疫反应驱动的慢性呼吸道疾病。上皮来源的警报素，如胸腺基质淋巴细胞生成素（TSLP）、白细胞介素（IL）-33和IL-25，协同下游辅助性T细胞2型（Th2细胞）和2型固有淋巴细胞（ILC2s）以及其他免疫效应细胞的激活。虽然这些警报素是对吸入性触发因素，如过敏原、呼吸道病原体或颗粒物作出反应而产生的，但气道上皮细胞产生的警报素不成比例会导致哮喘加重。由于警报素在2型炎症级联反应的上游产生，了解这些警报素的调控和表达途径对于进一步探索治疗哮喘患者的新疗法至关重要。本综述强调气道上皮和上皮来源的警报素在哮喘发病机制中的关键作用，并突出了以警报素为靶点作为一种有前景的治疗方法来改善哮喘患者预后的潜力。
