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 β₂‐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.

中文翻译：

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亚秒自发儿茶酚胺在离体肠系膜淋巴结中释放。

在过去的几年中，测量神经化学调节的免疫动力学，尤其是在肠道中，已经引起了越来越多的关注，因为它对胃肠道炎症，神经变性甚至抑郁症具有重要意义。交感神经原能神经支配胃肠道和驻留的免疫器官，包括肠系膜淋巴结（MLN）和派尔氏淋巴结。先前的研究表明，MLN的神经元输入在神经免疫突触中释放去甲肾上腺素（NE），以调节免疫功能。当前的免疫学技术在完整的淋巴器官的特定区域内，尚无适当的时间或空间分辨率来实时监测此动态过程。实时监控完整免疫器官内的动态神经信号，可以促进对神经免疫交流的更深入了解，并可以阐明快速免疫调节的机制。在这里，我们通过结合使用C57BL / 6小鼠活MLN切片中的快速扫描循环伏安法（FSCV）进行实时神经化学检测来克服这一技术障碍。我们发现，在MLN的T细胞区中，快速，自发的儿茶酚胺瞬变大约为数百纳摩尔，快速（几秒钟）和频繁（每20秒）。我们证明了β MLN的T细胞区中的自发儿茶酚胺瞬变大约为数百纳摩尔，快速（几秒钟）和频繁（每20秒）。我们证明了β MLN的T细胞区中的自发儿茶酚胺瞬变大约为数百纳摩尔，快速（几秒钟）和频繁（每20秒）。我们证明了β₂肾上腺素能受体和经典的儿茶酚胺转运蛋白（DAT和NET）在MLN的瞬时调节中起次要作用，提示神经免疫突触的调节非常复杂，需要进一步的机理研究。总体而言，这些发现提供了MLN中快速神经化学事件的直接证据，这可能会对我们对肠道神经化学调节的免疫调节的理解产生重大影响。