近日，浙江大学医学院教授方向明及其小组提出了从GABA能神经元到ADRB2⁺间质巨噬细胞的脑-肺信号促进肺部炎症反应。2025年6月3日出版的《免疫学》杂志发表了这项成果。

研究团队发现中央杏仁核（CeA）的GABA能神经元在严重肺炎期间高度激活，这在很大程度上促成了炎症和肺损伤。抑制CeA -GABA能神经元可减轻致死性肺炎小鼠的细胞因子风暴并提高存活率。该课题组研究人员发现了一条连接大脑和肺部的CeA-吻侧腹外侧髓质-交感神经通路，它增强了去甲肾上腺素（NE）的释放并放大了炎症信号。肺交感神经（PSNs）周围的β2-肾上腺素能受体(ADRB2)⁺间质巨噬细胞亚群对NE升高有反应，这加重了严重肺炎期间的炎症和肺损伤。特异性抑制PSNs和ADRB2信号可改善重症肺炎的预后。他们的研究确定了一种关键的脑-肺交感信号，控制巨噬细胞介导的肺部炎症反应，这可能被用作严重肺炎的治疗策略。

研究人员表示，严重肺炎主要由肺细胞因子风暴主导，但这一过程是否受脑-肺轴控制尚不清楚。

附：英文原文

Title: A brain-to-lung signal from GABAergic neurons to ADRB2+ interstitial macrophages promotes pulmonary inflammatory responses

Author: Weijue Li, Haoyang Zhu, Xiaoyu Zou, Hui Ye, Jia Zhong, Shasha Xiang, Yi Lou, Jiali Mao, Lingyun Qi, Xiawei Hu, Yan Zhang, Jinchao Hou, Bingduo Wang, Christian Bode, Andreas Hoeft, Xuekun Li, Kai Zhang, Marco Colonna, Xiangming Fang

Issue&Volume: 2025-06-03

Abstract: Severe pneumonia is predominantly caused by cytokine storms in the lung, but whether this process is controlled by the brain-lung axis remains unclear. Here, we found that GABAergic neurons in the central amygdala (CeA) were highly activated during severe pneumonia, which substantially contributed to inflammation and lung injury. Inhibition of CeA GABAergic neurons mitigated cytokine storms and improved survival rates in lethal pneumonia in mice. We uncovered a CeA-rostral ventrolateral medulla-sympathetic neural pathway connecting the brain to the lung, which enhanced norepinephrine (NE) release and amplified inflammatory signals. A subpopulation of β2-adrenergic receptor (ADRB2)+ interstitial macrophages surrounding the pulmonary sympathetic nerves (PSNs) responded to elevated NE, which aggravated inflammation and lung injury during severe pneumonia. Specific inhibition of PSNs and ADRB2 signaling improved the outcomes of severe pneumonia. Our study identifies a crucial brain-to-lung sympathetic signal controlling macrophage-mediated lung inflammatory responses, which could be harnessed as a therapeutic strategy for severe pneumonia.

DOI: 10.1016/j.immuni.2025.05.005

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00226-2