Han Jinming, Harris Robert A, Zhang Xing-Mei
Applied Immunology and Immunotherapy, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital at Solna, CMM L8:04, Karolinska Sjukhuset, S-171 76, Stockholm, Sweden.
Mol Brain. 2017 Jun 19;10(1):25. doi: 10.1186/s13041-017-0307-x.
Microglia are the principal resident immune cells in the central nervous system and are believed to be versatile players in both inflammatory and physiological contexts. On the one hand, in order to safeguard the microenvironment microglia can be rapidly activated by contact with microbial products or cell debris, thereby exerting the functions of innate immunity via phagocytosis and secretion of cytokines and chemokines. Conversely, microglia can also assist in brain development, synaptic plasticity and neural repair through the production of neurotrophic factors and clearance of myelin debris. It is now well accepted that the dysfunction of microglia and microglia-induced neuroinflammation are implicated in the occurrence and progression of many neurological diseases. Although the past decade has witnessed major progress in understanding of multi-tasking microglia, what remains largely enigmatic is the relative importance of microglia at different disease stages and how microglia should be targeted for optimal therapeutic efficacy. Notably, microglia depletion through genetic targeting or pharmacological therapies can be viewed as effective tools to stimulate new microglia to repopulate the central nervous system. Microglia depletion and subsequent repopulation at defined stages in various experimental animal model disorders allow us to extend our knowledge of molecular mechanisms, thus holding promise for designing strategies to resolve neuroinflammation and promote recovery. Herein we highlight the highly plastic and diverse phenotypes of microglia and outline the lessons learned from microglia depletion approaches.
小胶质细胞是中枢神经系统中主要的常驻免疫细胞，被认为在炎症和生理环境中都起着多方面的作用。一方面，为了维护微环境，小胶质细胞可通过与微生物产物或细胞碎片接触而迅速被激活，从而通过吞噬作用以及细胞因子和趋化因子的分泌发挥固有免疫功能。相反，小胶质细胞还可通过产生神经营养因子和清除髓磷脂碎片来协助大脑发育、突触可塑性和神经修复。现在人们普遍认为，小胶质细胞功能障碍和小胶质细胞诱导的神经炎症与许多神经疾病的发生和发展有关。尽管在过去十年中，对具有多种功能的小胶质细胞的认识取得了重大进展，但在不同疾病阶段小胶质细胞的相对重要性以及如何针对小胶质细胞实现最佳治疗效果在很大程度上仍然是个谜。值得注意的是，通过基因靶向或药物疗法清除小胶质细胞可被视为刺激新的小胶质细胞重新填充中枢神经系统的有效工具。在各种实验动物模型疾病的特定阶段进行小胶质细胞清除和随后的重新填充，使我们能够扩展对分子机制的认识，从而有望设计出解决神经炎症和促进恢复的策略。在此，我们强调小胶质细胞高度可塑性和多样的表型，并概述从小胶质细胞清除方法中学到的经验教训。
