Cholinergic modulation of the immune system presents new approaches for treating inflammation.
Cholinergic modulation of the immune system presents new approaches for treating inflammation.
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DOI：
10.1016/j.pharmthera.2017.05.002
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发表时间：
2017-11
影响因子：
13.5
通讯作者：
Hoover DB
中科院分区：
文献类型：
--
作者：
Hoover DB
神经系统和免疫系统在体内分布广泛且重叠，这些无处不在的系统之间的相互作用是神经免疫学领域的核心。在过去的二十年中，我们对通过自主神经系统介导免疫功能的中枢调节的神经解剖学、细胞和分子机制的理解出现了爆炸性增长。该领域发展的一个主要催化剂是发现迷走神经刺激（VNS）可显着减弱实验动物内毒素引起的全身炎症反应。这种作用是通过乙酰胆碱（ACh）刺激脾巨噬细胞上的烟碱受体介导的。因此，该回路被称为“胆碱能抗炎通路”。随后的工作确定 α7 烟碱 ACh 受体 (α7nAChR) 是减弱巨噬细胞和树突状细胞促炎细胞因子释放的关键靶点。进一步的研究发现，刺激脾巨噬细胞上α7受体的ACh来源是脾脏内的胆碱能T细胞，而不是胆碱能神经细胞。鉴于炎症在许多疾病过程中发挥的重要作用，胆碱能抗炎机制正在从基础科学的角度进行深入研究，并在炎症性肠病和类风湿性关节炎等疾病的动物模型的转化研究中进行深入研究。这项基础工作已经催生了多项临床试验，检验 VNS 和胆碱能疗法在人类炎症性疾病中的功效。本综述概述了胆碱能抗炎反应的基本和转化方面以及作用于 α7nAChR 的药物的相关药理学。
The nervous system and immune system have broad and overlapping distributions in the body, and interactions of these ubiquitous systems are central to the field of neuroimmunology. Over the past two decades, there has been explosive growth in our understanding of neuroanatomical, cellular, and molecular mechanisms that mediate central modulation of immune functions through the autonomic nervous system. A major catalyst for growth in this field was the discovery that vagal nerve stimulation (VNS) caused a prominent attenuation of the systemic inflammatory response evoked by endotoxin in experimental animals. This effect was mediated by acetylcholine (ACh) stimulation of nicotinic receptors on splenic macrophages. Hence, the circuit was dubbed the “cholinergic anti-inflammatory pathway”. Subsequent work identified the α7 nicotinic ACh receptor (α7nAChR) as the crucial target for attenuation of pro-inflammatory cytokine release from macrophages and dendritic cells. Further investigation made the important discovery that cholinergic T cells within the spleen and not cholinergic nerve cells were the source of ACh that stimulated α7 receptors on splenic macrophages. Given the important role that inflammation plays in numerous disease processes, cholinergic anti-inflammatory mechanisms are under intensive investigation from a basic science perspective and in translational studies of animal models of diseases such as inflammatory bowel disease and rheumatoid arthritis. This basic work has already fostered several clinical trials examining the efficacy of VNS and cholinergic therapeutics in human inflammatory diseases. This review provides an overview of basic and translational aspects of the cholinergic anti-inflammatory response and relevant pharmacology of drugs acting at the α7nAChR.
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目前对创伤和感染免疫反应机制的看法。
DOI：
10.5114/ceji.2015.52835
发表时间：
2015
期刊：
Central-European journal of immunology
影响因子：
--
作者：
Binkowska AM;Michalak G;Słotwiński R
通讯作者：
Słotwiński R
影响因子：
3.1
作者：
Akaike, Akinori;Takada-Takatori, Yuki;Izumi, Yasuhiko
通讯作者：
Izumi, Yasuhiko
影响因子：
3.5
作者：
Bonaz, B.;Sinniger, V.;Pellissier, S.
通讯作者：
Pellissier, S.
影响因子：
2.7
作者：
Bratton, B. O.;Martelli, D.;McAllen, R. M.
通讯作者：
McAllen, R. M.
DOI：
10.1007/s11481-015-9601-5
发表时间：
2015-09
期刊：
Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology
影响因子：
--
作者：
Báez-Pagán CA;Delgado-Vélez M;Lasalde-Dominicci JA
通讯作者：
Lasalde-Dominicci JA