A vagal reflex evoked by airway closure.
A vagal reflex evoked by airway closure.
复制标题
气道关闭引起的迷走神经反射。
DOI：
10.1038/s41586-024-07144-2
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发表时间：
2024
期刊：
影响因子：
64.8
通讯作者：
Liberles,StephenD
中科院分区：
文献类型：
--
作者：
Schappe,MichaelS;Brinn,PhilipA;Joshi,NarendraR;Greenberg,RachelS;Min,Soohong;Alabi,AbdulRasheedA;Zhang,Chuchu;Liberles,StephenD
呼吸道的完整性必须在整个生命过程中持续保持。感觉神经元防止气道阻塞，并在每时每刻的基础上，制定重要的反射，以维持呼吸功能。在许多呼吸系统疾病中，肺容量减少是常见的并且危及生命，并且肺萎陷可以由胸壁创伤、气胸或气道压迫急性诱发。在这里，我们描述了迷走神经的神经元反射引起的气道关闭，导致喘气。在体内迷走神经节成像显示专用的感觉神经元，检测气道压缩，但不是气道拉伸。表达PVALB的迷走神经元介导气道闭合反应，并支配称为神经上皮小体（NEB）的肺上皮细胞簇。刺激NEB或迷走神经PVALB神经元在没有气道威胁的情况下诱发喘息，而消融NEB或迷走神经PVALB神经元消除了响应于气道关闭的喘息。单细胞RNA测序显示NEBs均匀表达机械感受器PIEZO 2，靶向敲除NEBs中的Piezo 2消除了对气道闭合的反应。对NEB进行Hering-Breuer吸气反射，这表明离散的末端结构检测气道闭合和充气。与默克尔细胞参与触觉相似，NEB是表达PIEZO 2的上皮细胞，而且对于肺机械感觉的一个方面至关重要。这些发现扩展了我们对呼吸道神经元多样性的理解，并揭示了一个专门的迷走神经通路，它可以检测呼吸道关闭，以帮助保护呼吸功能。
Airway integrity must be continuously maintained throughout life. Sensory neurons guard against airway obstruction and, on a moment-by-moment basis, enact vital reflexes to maintain respiratory function,. Decreased lung capacity is common and life-threatening across many respiratory diseases, and lung collapse can be acutely evoked by chest wall trauma, pneumothorax or airway compression. Here we characterize a neuronal reflex of the vagus nerve evoked by airway closure that leads to gasping. In vivo vagal ganglion imaging revealed dedicated sensory neurons that detect airway compression but not airway stretch. Vagal neurons expressing PVALB mediate airway closure responses and innervate clusters of lung epithelial cells called neuroepithelial bodies (NEBs). Stimulating NEBs or vagal PVALB neurons evoked gasping in the absence of airway threats, whereas ablating NEBs or vagal PVALB neurons eliminated gasping in response to airway closure. Single-cell RNA sequencing revealed that NEBs uniformly express the mechanoreceptor PIEZO2, and targeted knockout ofPiezo2in NEBs eliminated responses to airway closure. NEBs were dispensable for the Hering–Breuer inspiratory reflex, which indicated that discrete terminal structures detect airway closure and inflation. Similar to the involvement of Merkel cells in touch sensation,, NEBs are PIEZO2-expressing epithelial cells and, moreover, are crucial for an aspect of lung mechanosensation. These findings expand our understanding of neuronal diversity in the airways and reveal a dedicated vagal pathway that detects airway closure to help preserve respiratory function.