美国加州大学Xin Sun团队近期取得重要工作进展，他们研究提出脑干Dbh⁺神经元能够控制过敏原诱导的气道高反应性。相关研究成果2024年7月10日在线发表于《自然》杂志上。

据介绍，反复接触过敏原引发的气道过度收缩，也称为高反应性，是哮喘的标志。尽管已知迷走神经感觉神经元在过敏原诱导的高反应性中起作用，但下游节点的身份仍然知之甚少。

研究人员绘制了从肺部到脑干再回到肺部的完整过敏原回路。反复暴露于吸入性过敏原的小鼠以肥大细胞、白细胞介素-4（IL-4）和迷走神经依赖的方式激活了孤束（nTS）神经元的核。单核RNA测序，随后在基线和过敏原挑战时进行RNAscope分析，表明Dbh⁺ nTS群体被优先激活。Dbh⁺ nTS神经元的消融或化学灭活会减弱高反应性，而化学发生激活则会促进高反应性。

病毒追踪表明，Dbh⁺ nTS神经元投射到伏隔核（NA），NA神经元是将过敏原信号传递给直接驱动气道收缩的节后神经元所必需和足够的。将去甲肾上腺素拮抗剂输送到NA可以减弱高反应性，表明去甲肾上腺素是Dbh⁺ nTS和NA之间的递质。

总之，这些发现提供了典型过敏原反应回路关键节点的分子、解剖学和功能定义。这些资源告诉人们如何使用神经调节来控制过敏原诱导的气道高反应性。

附：英文原文

Title: Brainstem Dbh+ neurons control allergen-induced airway hyperreactivity

Author: Su, Yujuan, Xu, Jinhao, Zhu, Ziai, Chin, Jisun, Xu, Le, Yu, Haoze, Nudell, Victoria, Dash, Barsha, Moya, Esteban A., Ye, Li, Nimmerjahn, Axel, Sun, Xin

Issue&Volume: 2024-07-10

Abstract: Exaggerated airway constriction triggered by repeated exposure to allergen, also called hyperreactivity, is a hallmark of asthma. Whereas vagal sensory neurons are known to function in allergen-induced hyperreactivity1,2,3, the identity of downstream nodes remains poorly understood. Here we mapped a full allergen circuit from the lung to the brainstem and back to the lung. Repeated exposure of mice to inhaled allergen activated the nuclei of solitary tract (nTS) neurons in a mast cell-, interleukin-4 (IL-4)- and vagal nerve-dependent manner. Single-nucleus RNA sequencing, followed by RNAscope assay at baseline and allergen challenges, showed that a Dbh+ nTS population is preferentially activated. Ablation or chemogenetic inactivation of Dbh+ nTS neurons blunted hyperreactivity whereas chemogenetic activation promoted it. Viral tracing indicated that Dbh+ nTS neurons project to the nucleus ambiguus (NA) and that NA neurons are necessary and sufficient to relay allergen signals to postganglionic neurons that directly drive airway constriction. Delivery of noradrenaline antagonists to the NA blunted hyperreactivity, suggesting noradrenaline as the transmitter between Dbh+ nTS and NA. Together, these findings provide molecular, anatomical and functional definitions of key nodes of a canonical allergen response circuit. This knowledge informs how neural modulation could be used to control allergen-induced airway hyperreactivity.

DOI: 10.1038/s41586-024-07608-5

Source: https://www.nature.com/articles/s41586-024-07608-5