Huerta Tomás S, Chen Adrian C, Chaudhry Saher, Tynan Aisling, Morgan Timothy, Park Kicheon, Adamovich-Zeitlin Richard, Haider Bilal, Li Jian Hua, Nagpal Mitali, Zanos Stavros, Pavlov Valentin A, Brines Michael, Zanos Theodoros P, Chavan Sangeeta S, Tracey Kevin J, Chang Eric H
Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA.
Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA.
Nat Commun. 2025 Apr 24;16(1):3840. doi: 10.1038/s41467-025-59248-6.
The nervous system coordinates with the immune system to detect and respond to harmful stimuli. Inflammation is a universal response to injury and infection that involves the release of cytokines. While it is known that information about cytokines is transmitted from the body to the brain, how the nervous system encodes specific cytokines in the form of neural activity is not well understood. Using in vivo calcium imaging, we show that vagal sensory neurons within the nodose ganglia exhibit distinct real-time neuronal responses to inflammatory cytokines. Some neurons respond selectively to individual cytokines, while others encode multiple cytokines with distinct activity patterns. In male mice with induced colitis, inflammation increased the baseline activity of these neurons but decreased responsiveness to specific cytokines, reflecting altered neural excitability. Transcriptomic analysis of vagal ganglia from colitis mice revealed downregulation of cytokine signaling pathways, while neuronal activity pathways were upregulated. Thus, nodose ganglia neurons perform real-time encoding of cytokines at the first neural station in a body-brain axis, providing a new framework for studying the dynamic nature of neuroimmune communication.
神经系统与免疫系统协同工作，以检测有害刺激并做出反应。炎症是对损伤和感染的一种普遍反应，涉及细胞因子的释放。虽然已知有关细胞因子的信息会从身体传递到大脑，但神经系统如何以神经活动的形式编码特定细胞因子尚不清楚。通过体内钙成像，我们发现结状神经节内的迷走感觉神经元对炎性细胞因子表现出独特的实时神经元反应。一些神经元对单个细胞因子有选择性反应，而其他神经元则以不同的活动模式编码多种细胞因子。在诱导性结肠炎的雄性小鼠中，炎症增加了这些神经元的基线活动，但降低了对特定细胞因子的反应性，反映出神经兴奋性的改变。对结肠炎小鼠迷走神经节的转录组分析显示细胞因子信号通路下调，而神经元活动通路上调。因此，结状神经节神经元在体-脑轴的第一个神经站对细胞因子进行实时编码，为研究神经免疫通讯的动态性质提供了一个新框架。
