TY - T1的昼夜哮喘气道反应由REV-ERB封闭的αJF -欧洲呼吸杂志》乔和J - 10.1183/13993003.02407 -2019欧元六世- 56 - 6 SP - 1902407 AU -杜灵顿,汉娜J . AU - Krakowiak卡罗丽娜AU -梅耶尔,彼得AU -贝格利,尼古拉AU -梅德斯通,罗伯特。非盟-鹅,劳伦斯AU -吉布斯Julie E. AU - Blaikley, John F. AU - Gregory, Lisa G. AU - Lloyd, Clare M. AU - Loudon, Andrew S.I. AU - Ray，生物钟有力地调节炎症，已知时钟蛋白rev - erba作为炎症反应的抑制因子发挥着关键作用。哮喘是一种具有强烈时间节律的呼吸道炎症性疾病。气道高反应性(AHR)是哮喘的主要特征;然而，尚不清楚这是否在时钟控制之下。目的探讨过敏性AHR是否受时钟蛋白REV-ERBα的调控。方法采用鼻内屋尘螨(HDM)变应原激发模型，分别于黎明和黄昏照射小鼠，测定其对乙酰胆碱的AHR。主要结果野生型小鼠在体内和体外精确切片显示出明显不同的AHR反应时间(黄昏/活动期开始时达到最大值)。在缺乏生物钟基因rev - erba的小鼠中，日间时间对AHR的影响被消除，这表明这种对哮喘反应的影响可能是通过昼夜时钟介导的。 We suggest that muscarinic receptors one (Chrm 1) and three (Chrm 3) may play a role in this pathway.Conclusions We identify a novel circuit regulating a core process in asthma, potentially involving circadian control of muscarinic receptor expression, in a REV-ERBα dependent fashion.Clinical implication These insights suggest the importance of considering the timing of drug administration in clinic trials and in clinical practice (chronotherapy).REV-ERBα gates airway hyper-responsiveness by time of day. Future asthma therapies should aim to dose anti-muscarinic agents at the most efficacious time of day (chronotherapy) and modulate the molecular clock https://bit.ly/37qY4sC ER -