Department of Medicine, McMaster University, Hamilton, ON L8N 3Z5, Canada.
Cells. 2022 Mar 24;11(7):1105. doi: 10.3390/cells11071105.
The airway epithelium is the first line of defense for the lungs, detecting inhaled environmental threats through pattern recognition receptors expressed transmembrane or intracellularly. Activation of pattern recognition receptors triggers the release of alarmin cytokines IL-25, IL-33, and TSLP. These alarmins are important mediators of inflammation, with receptors widely expressed in structural cells as well as innate and adaptive immune cells. Many of the key effector cells in the allergic cascade also produce alarmins, thereby contributing to the airways disease by driving downstream type 2 inflammatory processes. Randomized controlled clinical trials have demonstrated benefit when blockade of TSLP and IL-33 were added to standard of care medications, suggesting these are important new targets for treatment of asthma. With genome-wide association studies demonstrating associations between single-nucleotide polymorphisms of the TSLP and IL-33 gene and risk of asthma, it will be important to understand which subsets of asthma patients will benefit most from anti-alarmin therapy.
气道上皮是肺部的第一道防线，通过表达跨膜或细胞内的模式识别受体来检测吸入的环境威胁。模式识别受体的激活触发警报素细胞因子 IL-25、IL-33 和 TSLP 的释放。这些警报素是炎症的重要介质，其受体广泛表达于结构细胞以及固有和适应性免疫细胞中。过敏级联反应中的许多关键效应细胞也产生警报素，从而通过驱动下游 2 型炎症过程来导致气道疾病。随机对照临床试验表明，当 TSLP 和 IL-33 的阻断作用被添加到标准护理药物中时，会带来益处，这表明它们是治疗哮喘的重要新靶点。全基因组关联研究表明，TSLP 和 IL-33 基因的单核苷酸多态性与哮喘风险之间存在关联，因此了解哪些哮喘患者亚群将从抗警报素治疗中获益最大将非常重要。
