Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, Italy.
CNR Institute of Neuroscience, 20129 Milan, Italy.
Cells. 2020 Sep 23;9(10):2145. doi: 10.3390/cells9102145.
Tumor necrosis factor (TNF) is a pleiotropic cytokine powerfully influencing diverse processes of the central nervous system (CNS) under both physiological and pathological conditions. Here, we analyze current literature describing the molecular processes involved in TNF synthesis and release from microglia, the resident immune cells of the CNS and the main source of this cytokine both in brain development and neurodegenerative diseases. A special attention has been given to the unconventional vesicular pathway of TNF, based on the emerging role of microglia-derived extracellular vesicles (EVs) in the propagation of inflammatory signals and in mediating cell-to-cell communication. Moreover, we describe the contribution of microglial TNF in regulating important CNS functions, including the neuroinflammatory response following brain injury, the neuronal circuit formation and synaptic plasticity, and the processes of myelin damage and repair. Specifically, the available data on the functions mediated by microglial EVs carrying TNF have been scrutinized to gain insights on possible novel therapeutic strategies targeting TNF to foster CNS repair.
肿瘤坏死因子（TNF）是一种多功能细胞因子，在生理和病理条件下强烈影响中枢神经系统（CNS）的多种过程。在这里，我们分析了描述 TNF 从小胶质细胞合成和释放的分子过程的当前文献，小胶质细胞是 CNS 的常驻免疫细胞，也是这种细胞因子在脑发育和神经退行性疾病中的主要来源。特别关注了 TNF 的非经典囊泡途径，这是基于小胶质细胞衍生的细胞外囊泡（EVs）在炎症信号传播和介导细胞间通讯中的新兴作用。此外，我们描述了小胶质细胞 TNF 在调节重要 CNS 功能中的贡献，包括脑损伤后的神经炎症反应、神经元回路形成和突触可塑性以及髓鞘损伤和修复过程。具体来说，我们仔细研究了携带 TNF 的小胶质细胞 EVs 介导的功能的可用数据，以深入了解针对 TNF 促进 CNS 修复的可能新的治疗策略。
