Department of Cell Biology, Physiology and Immunology, Institute of Neuroscience. Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain.
Department of Cell Biology, Physiology and Immunology, Institute of Neuroscience. Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain.
Neuroscience. 2019 May 1;405:118-136. doi: 10.1016/j.neuroscience.2018.10.030. Epub 2018 Oct 24.
Microglia are considered to be the resident macrophages of the CNS and main effector of immune brain function. Due to their essential role in the regulation of neuroinflammatory response, microglia constitute an important target for neurological diseases, such as multiple sclerosis, Alzheimer's or Parkinson's disease. The communication between neurons and microglia contributes to a proper maintenance of homeostasis in the CNS. Research developed in the last decade has demonstrated that this interaction is mediated by "Off-signals" - molecules exerting immune inhibition - and "On signals" - molecules triggering immune activation. Among "Off signals", molecular pair CD200 and its CD200R receptor, expressed mainly in the membrane of neurons and microglia, respectively, have centered our attention due to its unexplored and powerful immunoregulatory functions. In this review, we will offer an updated global view of the CD200-CD200R role in the microglia-neuron crosstalk during homeostasis and neuroinflammation. Specifically, the effects of CD200-CD200R in the inhibition of pro-inflammatory microglial activation will be explained, and their involvement in other functions such as homeostasis preservation, tissue repair, and brain aging, among others, will be pointed out. In addition, we will depict the effects of CD200-CD200R uncoupling in the etiopathogenesis of autoimmune and neurodegenerative diseases. Finally, we will explore how to translate the scientific evidence of CD200-CD200R interaction into possible clinical therapeutic strategies to tackle neuroinflammatory CNS diseases.
小胶质细胞被认为是中枢神经系统（CNS）的固有巨噬细胞，也是免疫脑功能的主要效应细胞。由于其在调节神经炎症反应中的重要作用，小胶质细胞成为多种神经疾病（如多发性硬化症、阿尔茨海默病或帕金森病）的重要靶点。神经元与小胶质细胞之间的通讯有助于中枢神经系统（CNS）的内环境稳定。过去十年的研究表明，这种相互作用是由“负信号”（发挥免疫抑制作用的分子）和“正信号”（触发免疫激活的分子）介导的。在“负信号”中，分子对 CD200 和其 CD200R 受体，分别主要表达在神经元和小胶质细胞膜上，由于其未被探索的强大免疫调节功能，引起了我们的关注。在这篇综述中，我们将提供一个关于 CD200-CD200R 在稳态和神经炎症中小胶质细胞-神经元相互作用中的作用的最新全面观点。具体来说，将解释 CD200-CD200R 抑制促炎小胶质细胞激活的作用，并指出它们在其他功能中的参与，如维持内环境稳定、组织修复和大脑衰老等。此外，我们将描述 CD200-CD200R 解耦在自身免疫和神经退行性疾病发病机制中的作用。最后，我们将探讨如何将 CD200-CD200R 相互作用的科学证据转化为可能的临床治疗策略，以应对神经炎症性中枢神经系统疾病。
