J Clin Invest. 2020 Apr 1;130(4):1632-1634. doi: 10.1172/JCI135949.
Cystic fibrosis (CF) is a multisystem disorder, but progressive inflammatory lung disease causes the greatest burden of morbidity and death. Recent translational and mechanistic studies of samples from patients, and observations in animal models, indicate that platelets may drive lung injury and contribute to dysregulated host defense in CF lung disease. In this issue of the JCI, Ortiz-Muñoz and Yu et al. explored the role that the cystic fibrosis transmembrane conductance regulator (CFTR) plays in platelet-related inflammation. The authors used mouse and human model systems to show that CFTR dysfunction in platelets increased calcium entry though the transient receptor potential cation channel 6 (TRPC6), causing hyperactivation and consequent experimental lung inflammation. The study persuasively suggests that platelets are critical thromboinflammatory effector cells in CF lung disease. In the context of platelet-related organ injury seen in a variety of other diseases and syndromes, platelets may also contribute to nonpulmonary manifestations and comorbidities of CF.
囊性纤维化 (CF) 是一种多系统疾病,但进行性炎症性肺部疾病导致发病率和死亡率的最大负担。最近对来自患者的样本的转化和机制研究,以及在动物模型中的观察,表明血小板可能驱动肺部损伤,并导致 CF 肺部疾病中失调的宿主防御。在本期 JCI 中,Ortiz-Muñoz 和 Yu 等人探讨了囊性纤维化跨膜电导调节因子 (CFTR) 在血小板相关炎症中所起的作用。作者使用小鼠和人类模型系统表明,血小板中 CFTR 功能障碍会增加钙通过瞬时受体电位阳离子通道 6 (TRPC6) 的进入,导致血小板过度激活和随后的实验性肺部炎症。该研究有力地表明,血小板是 CF 肺部疾病中关键的血栓炎症效应细胞。在其他各种疾病和综合征中观察到的与血小板相关的器官损伤的背景下,血小板也可能导致 CF 的非肺部表现和合并症。