Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University, School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
AMED-CREST, Japan Agency for Medical Research and Development, Tokyo 100-0004, Japan.
Int Immunol. 2022 Sep 6;34(9):475-484. doi: 10.1093/intimm/dxac033.
It has long been assumed that the nervous system exerts distinct effects on immune functions, given the large number of immune disorders that are affected by mental stress. In fact, many different immune cells have been shown to possess a wide variety of neurotransmitter receptors and receive signals from various neurotransmitters, including acetylcholine and noradrenaline. Compared with the findings on local neuroimmune interactions, limited experimental techniques have so far failed to capture a comprehensive overview of neuroimmune interactions between distant organs and the autonomic nervous system in vivo, and the molecular mechanisms underlying local immune regulation of the nervous system have long remained unclear. However, the recent rapid progress in genetic recombination, microscopy and single-cell analysis has deepened our understanding of the anatomical and physiological functions of peripheral nerves at each organ to which they belong. Furthermore, the development of optogenetic and chemogenetic methods has enabled the artificial modulation of specific neuronal activities, and there has been remarkable progress in elucidation of the interaction between nerves and immune cells in vivo, particularly in barrier organs such as the gastrointestinal tract, respiratory tract and skin. This review focuses on the immunoregulatory mechanisms governed by the autonomic nervous system and outlines the latest findings in the regulation of enteric and hepatic immunity by the nervous system.
长期以来，人们一直认为神经系统对免疫功能有显著影响，因为许多免疫紊乱都受到精神压力的影响。事实上，许多不同的免疫细胞已经被证明拥有各种各样的神经递质受体，并接收来自各种神经递质的信号，包括乙酰胆碱和去甲肾上腺素。与局部神经免疫相互作用的研究结果相比，目前有限的实验技术还无法全面了解体内远处器官和自主神经系统之间的神经免疫相互作用，而神经系统局部免疫调节的分子机制长期以来一直不清楚。然而，近年来遗传重组、显微镜和单细胞分析技术的快速发展，加深了我们对每个器官所属外周神经的解剖和生理功能的理解。此外，光遗传学和化遗传学方法的发展使得对特定神经元活动的人工调节成为可能，并且在阐明体内神经和免疫细胞之间的相互作用方面取得了显著进展，特别是在胃肠道、呼吸道和皮肤等屏障器官中。这篇综述重点介绍了自主神经系统控制的免疫调节机制，并概述了神经系统对肠道和肝脏免疫的最新调节发现。
