Manipulation of the inflammatory reflex as a therapeutic strategy.
Manipulation of the inflammatory reflex as a therapeutic strategy.
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DOI：
10.1016/j.xcrm.2022.100696
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发表时间：
2022-07-19
影响因子：
14.3
通讯作者：
Donnelly, Seamas C.
中科院分区：
文献类型：
--
作者：
Kelly, Mark J.;Breathnach, Caitriona;Tracey, Kevin J.;Donnelly, Seamas C.
胆碱能抗炎通路是炎症反射的传出臂，是中枢神经系统调节外周免疫反应的神经回路。通过迷走神经和脾神经传递的信号通过胆碱乙酰转移酶(Choline acetyltransferase, ChAT)+ T细胞产生的乙酰胆碱下调表达α7烟碱受体的巨噬细胞的炎症行为。利用转基因动物、胆碱能激动剂、迷走神经切开术和迷走神经刺激进行的临床前研究已经证明了该途径在许多炎症性疾病中的作用和治疗潜力。在这篇综述中，我们总结了关于炎症反射的理解。我们还展示了临床前研究结果如何转化为有希望的临床试验，我们特别关注利用胆碱能抗炎途径用于临床的创新生物电子方法。越来越多的证据表明胆碱能通路具有显著的抗炎活性。Kelly及其同事回顾了神经炎症反射的现有知识，并强调了最近利用胆碱能抗炎途径作为针对疾病的治疗策略的工作。
The cholinergic anti-inflammatory pathway is the efferent arm of the inflammatory reflex, a neural circuit through which the CNS can modulate peripheral immune responses. Signals communicated via the vagus and splenic nerves use acetylcholine, produced by Choline acetyltransferase (ChAT)+ T cells, to downregulate the inflammatory actions of macrophages expressing α7 nicotinic receptors. Pre-clinical studies using transgenic animals, cholinergic agonists, vagotomy, and vagus nerve stimulation have demonstrated this pathway’s role and therapeutic potential in numerous inflammatory diseases. In this review, we summarize what is understood about the inflammatory reflex. We also demonstrate how pre-clinical findings are being translated into promising clinical trials, and we draw particular attention to innovative bioelectronic methods of harnessing the cholinergic anti-inflammatory pathway for clinical use. Increasing evidence has revealed the significant anti-inflammatory activity of the cholinergic pathway. Kelly and colleagues review the current knowledge of the neural inflammatory reflex and highlight recent work harnessing the cholinergic anti-inflammatory pathway as a therapeutic strategy targeting disease.
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