High-Dimensional Single-Cell Mapping of Central Nervous System Immune Cells Reveals Distinct Myeloid Subsets in Health, Aging, and Disease
High-Dimensional Single-Cell Mapping of Central Nervous System Immune Cells Reveals Distinct Myeloid Subsets in Health, Aging, and Disease
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DOI：
10.1016/j.immuni.2018.01.011
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发表时间：
2018-02-20
期刊：
影响因子：
32.4
通讯作者：
Becher, Burkhard
中科院分区：
文献类型：
--
作者：
Mrdjen, Dunja;Pavlovic, Anto;Becher, Burkhard
个别报告表明，中枢神经系统(CNS)包含多种免疫细胞类型，在组织内稳态、免疫防御和神经系统疾病中扮演不同的角色。绘制整个大脑的白细胞图谱一直是一个挑战，特别是在病理学中，表型变化和血源性细胞的涌入阻碍了反应性白细胞群体的明显区分。在这里，我们应用高维单细胞质量和荧光细胞术，以及遗传命运图谱系统，来识别、定位和表征哺乳动物中枢神经系统内的多个不同的免疫群体。利用这种方法，我们揭示了小胶质细胞、几个亚群的边界相关巨噬细胞和树突状细胞在稳定状态下共存于中枢神经系统，并在衰老过程中以及阿尔茨海默病和多发性硬化症模型中显示出免疫微环境中疾病特异性的变化。总之，这些数据和所描述的框架为研究中枢神经系统疾病的发病机制、潜在的生物标志物和治疗靶点提供了资源。
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.