Zhang Youming
National Heart and Lung Institute, Imperial College London, Dovehouse Street, London SW3 6LY, UK.
Chin Med J Pulm Crit Care Med. 2023 Sep 14;1(3):139-147. doi: 10.1016/j.pccm.2023.08.001. eCollection 2023 Sep.
Asthma is a chronic respiratory disease, and clinically, asthma exacerbations remain difficult to treat. The disease is caused by combinations of and interactions between genetic and environmental factors. Genomic and genetic approaches identified many novel genes to treat asthma and brought new insights into the disease. The products of the genes have functional roles in regulating physiological or pathophysiological processes in airway structural cells and immune system cells. Genetic factors also interact with environmental factors such as air pollutants, and bacterial and viral infections to trigger the disease. Thymic stromal lymphopoietin (), orosomucoid-like 3 (), and gasdermin B () are three genes identified by genetic studies to have a great potential as therapeutic targets of asthma. TSLP is an important driver of type 2 inflammation. ORMDL3 mediates cell stress, sphingolipid synthesis, and viral and bacterial infections. GSDMB regulates cell pyroptosis through its N and C terminals and can bind sulfatides to influence inflammatory response. Investigating inhibitors or modulators for these pathways would bring a new landscape for therapeutics of asthma in future.
哮喘是一种慢性呼吸道疾病，在临床上，哮喘急性发作仍然难以治疗。该疾病由遗传因素和环境因素的组合及相互作用引起。基因组学和遗传学方法鉴定出许多用于治疗哮喘的新基因，并为该疾病带来了新的见解。这些基因的产物在调节气道结构细胞和免疫系统细胞的生理或病理生理过程中具有功能性作用。遗传因素还与空气污染物、细菌和病毒感染等环境因素相互作用以引发该疾病。胸腺基质淋巴细胞生成素（TSLP）、类正五聚蛋白3（ORMDL3）和gasdermin B（GSDMB）是通过遗传学研究鉴定出的三个具有作为哮喘治疗靶点巨大潜力的基因。TSLP是2型炎症的重要驱动因子。ORMDL3介导细胞应激、鞘脂合成以及病毒和细菌感染。GSDMB通过其N端和C端调节细胞焦亡，并可结合硫苷脂以影响炎症反应。研究这些途径的抑制剂或调节剂将为未来哮喘治疗带来新的局面。
