Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
Department of Neuropathology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Immunity. 2018 Feb 20;48(2):380-395.e6. doi: 10.1016/j.immuni.2018.01.011. Epub 2018 Feb 6.
Individual reports suggest that the central nervous system (CNS) contains multiple immune cell types with diverse roles in tissue homeostasis, immune defense, and neurological diseases. It has been challenging to map leukocytes across the entire brain, and in particular in pathology, where phenotypic changes and influx of blood-derived cells prevent a clear distinction between reactive leukocyte populations. Here, we applied high-dimensional single-cell mass and fluorescence cytometry, in parallel with genetic fate mapping systems, to identify, locate, and characterize multiple distinct immune populations within the mammalian CNS. Using this approach, we revealed that microglia, several subsets of border-associated macrophages and dendritic cells coexist in the CNS at steady state and exhibit disease-specific transformations in the immune microenvironment during aging and in models of Alzheimer's disease and multiple sclerosis. Together, these data and the described framework provide a resource for the study of disease mechanisms, potential biomarkers, and therapeutic targets in CNS disease.
个体报告表明，中枢神经系统（CNS）包含多种具有不同功能的免疫细胞类型，在组织稳态、免疫防御和神经疾病中发挥作用。对整个大脑中的白细胞进行映射一直具有挑战性，特别是在病理学中，表型变化和血液来源细胞的涌入使得难以清楚地区分反应性白细胞群体。在这里，我们应用高维单细胞质量和荧光细胞术，同时结合遗传命运映射系统，来鉴定、定位和表征哺乳动物中枢神经系统内的多种不同的免疫群体。使用这种方法，我们揭示了在稳态下小胶质细胞、几种边界相关巨噬细胞和树突状细胞亚群共同存在于中枢神经系统中，并在衰老过程中和阿尔茨海默病和多发性硬化症的模型中表现出免疫微环境中的特定疾病转化。这些数据和所描述的框架为中枢神经系统疾病的发病机制、潜在生物标志物和治疗靶点的研究提供了资源。
