Department of Chemistry, University of Cincinnati, Cincinnati, OH, USA.
Department of Pediatrics, University of Cincinnati, College of Medicine and Division of Neurology, Cincinnati Children's Research Foundation, Cincinnati, OH, USA.
J Neurochem. 2020 Nov;155(4):417-429. doi: 10.1111/jnc.15115. Epub 2020 Jul 19.
Measuring the dynamics of neurochemical-regulated immunity, particularly in the gut, has been a growing interest over the last several years because of its important implications in gastrointestinal inflammation, neurodegeneration, and even depression. Sympathetic noradrenergic nerves innervate the gastrointestinal tract and resident immune organs, including the mesenteric lymph nodes (MLN) and Peyer's patches. Previous research has suggested that neuronal inputs in the MLN release norepinephrine (NE) at neural-immune synapses to regulate immune function. The current immunological techniques do not have the appropriate temporal or spatial resolution to monitor this dynamic process in real-time, within specific regions of intact lymphoid organs. Monitoring dynamic neural signaling within intact immune organs, in real-time, would facilitate a deeper understanding of neuroimmune communication and would allow the mechanism of rapid immunomodulation to be elucidated. Here, we overcome this technological barrier by coupling real-time neurochemical detection using fast-scan cyclic voltammetry (FSCV) in live MLN slices from C57BL/6 mice. We have discovered rapid, spontaneous catecholamine transients in the T-cell zone of the MLN which are on the order of a few hundred nanomolar, rapid (a few seconds), and frequent (every 20-s). We demonstrate that the β -adrenergic receptor and the classic catecholamine transporters (DAT and NET) play a minor role in transient regulation in the MLN suggesting that regulation at the neural-immune synapse is quite complicated and further mechanistic studies are needed. Overall, these findings provide direct evidence for rapid neurochemical events in the MLN which could have a major impact on our understanding of neurochemical-regulated immunomodulation in the gut.
近年来，测量神经化学调节免疫的动态变化，尤其是在肠道中，一直是人们关注的热点，因为它对胃肠道炎症、神经退行性变甚至抑郁症都有重要影响。交感去甲肾上腺素能神经支配胃肠道和固有免疫器官，包括肠系膜淋巴结（MLN）和派尔集合淋巴结。先前的研究表明，MLN 中的神经元输入在神经免疫突触释放去甲肾上腺素（NE）以调节免疫功能。目前的免疫技术没有适当的时间或空间分辨率来实时监测完整淋巴器官特定区域内的这种动态过程。实时监测完整免疫器官内的动态神经信号将有助于更深入地了解神经免疫通讯，并阐明快速免疫调节的机制。在这里，我们通过在来自 C57BL/6 小鼠的活体 MLN 切片中使用快速扫描循环伏安法（FSCV）进行实时神经化学检测，克服了这一技术障碍。我们发现 MLN 的 T 细胞区存在快速、自发的儿茶酚胺瞬变，其数量级为几百纳摩尔，速度很快（几秒钟），且频繁（每 20 秒一次）。我们证明β-肾上腺素能受体和经典儿茶酚胺转运体（DAT 和 NET）在 MLN 中的瞬变调节中作用较小，这表明神经免疫突触的调节非常复杂，需要进一步的机制研究。总的来说，这些发现为 MLN 中的快速神经化学事件提供了直接证据，这可能对我们理解肠道中神经化学调节的免疫调节有重大影响。
