Cotero Victoria, Kao Tzu-Jen, Graf John, Ashe Jeffrey, Morton Christine, Chavan Sangeeta S, Zanos Stavros, Tracey Kevin J, Puleo Christopher M
General Electric Research, Niskayuna, NY USA.
Feinstein Institutes for Medical Research, Manhasset, NY USA.
Bioelectron Med. 2020 Oct 23;6:21. doi: 10.1186/s42234-020-00056-2. eCollection 2020.
Peripheral nerve reflexes enable organ systems to maintain long-term physiological homeostasis while responding to rapidly changing environmental conditions. Electrical nerve stimulation is commonly used to activate these reflexes and modulate organ function, giving rise to an emerging class of therapeutics called bioelectronic medicines. Dogma maintains that immune cell migration to and from organs is mediated by inflammatory signals (i.e. cytokines or pathogen associated signaling molecules). However, nerve reflexes that regulate immune function have only recently been elucidated, and stimulation of these reflexes for therapeutic effect has not been fully investigated.
We utilized both electrical and ultrasound-based nerve stimulation to activate nerve pathways projecting to specific lymph nodes. Tissue and cell analysis of the stimulated lymph node, distal lymph nodes and immune organs is then utilized to measure the stimulation-induced changes in neurotransmitter/neuropeptide concentrations and immune cellularity in each of these sites.
In this report, we demonstrate that activation of nerves and stimulated release of neurotransmitters within a local lymph node results in transient retention of immune cells (e.g. lymphocytes and neutrophils) at that location. Furthermore, such stimulation results in transient changes in neurotransmitter concentrations at distal organs of the immune system, spleen and liver, and mobilization of immune cells into the circulation. This report will enable future studies in which stimulation of these long-range nerve connections between lymphatic and immune organs can be applied for clinical purpose, including therapeutic modulation of cellularity during vaccination, active allergic response, or active auto-immune disease.
外周神经反射使器官系统在应对快速变化的环境条件时能够维持长期的生理稳态。电神经刺激通常用于激活这些反射并调节器官功能，从而产生了一类新兴的治疗方法，即生物电子药物。传统观点认为，免疫细胞进出器官是由炎症信号（即细胞因子或病原体相关信号分子）介导的。然而，调节免疫功能的神经反射直到最近才被阐明，并且对这些反射进行治疗效果的刺激尚未得到充分研究。
我们利用电刺激和基于超声的神经刺激来激活投射到特定淋巴结的神经通路。然后对受刺激的淋巴结、远端淋巴结和免疫器官进行组织和细胞分析，以测量刺激引起的这些部位神经递质/神经肽浓度和免疫细胞数量的变化。
在本报告中，我们证明激活局部淋巴结内的神经并刺激神经递质释放会导致免疫细胞（如淋巴细胞和中性粒细胞）在该位置短暂滞留。此外，这种刺激会导致免疫系统远端器官（脾脏和肝脏）神经递质浓度的短暂变化，以及免疫细胞向循环系统的动员。本报告将为未来的研究提供可能，即刺激淋巴器官和免疫器官之间的这些远程神经连接可用于临床目的，包括在疫苗接种、活跃过敏反应或活跃自身免疫性疾病期间对细胞数量进行治疗性调节。
