Institute of Neuropathology, Faculty of Medicine, University of Freiburg, D-79106 Freiburg, Germany; email:
Center for Basics in NeuroModulation (NeuroModulBasics), Faculty of Medicine, University of Freiburg, D-79106 Freiburg, Germany.
Annu Rev Immunol. 2021 Apr 26;39:251-277. doi: 10.1146/annurev-immunol-093019-110159. Epub 2021 Feb 8.
The immune system of the central nervous system (CNS) consists primarily of innate immune cells. These are highly specialized macrophages found either in the parenchyma, called microglia, or at the CNS interfaces, such as leptomeningeal, perivascular, and choroid plexus macrophages. While they were primarily thought of as phagocytes, their function extends well beyond simple removal of cell debris during development and diseases. Brain-resident innate immune cells were found to be plastic, long-lived, and host to an outstanding number of risk genes for multiple pathologies. As a result, they are now considered the most suitable targets for modulating CNS diseases. Additionally, recent single-cell technologies enhanced our molecular understanding of their origins, fates, interactomes, and functional cell statesduring health and perturbation. Here, we review the current state of our understanding and challenges of the myeloid cell biology in the CNS and treatment options for related diseases.
中枢神经系统（CNS）的免疫系统主要由先天免疫细胞组成。这些细胞是高度特化的巨噬细胞，存在于实质中，称为小胶质细胞，或存在于 CNS 界面，如软脑膜、血管周围和脉络丛巨噬细胞。虽然它们最初被认为是吞噬细胞，但它们的功能远远超出了在发育和疾病过程中简单清除细胞碎片的范畴。研究发现，驻留于脑内的先天免疫细胞具有可塑性、长寿命，并携带多种病理学的大量风险基因。因此，它们现在被认为是调节 CNS 疾病的最适宜靶点。此外，最近的单细胞技术增强了我们对其在健康和干扰状态下起源、命运、相互作用组和功能细胞状态的分子理解。在这里，我们综述了目前对 CNS 中髓样细胞生物学的理解和挑战，以及相关疾病的治疗选择。
