High-Dimensional Single-Cell Mapping of Central Nervous System Immune Cells Reveals Distinct Myeloid Subsets in Health, Aging, and Disease

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 phenotypi...

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Veröffentlicht in:Immunity (Cambridge, Mass.) Jg. 48; H. 2; S. 380
Hauptverfasser: Mrdjen, Dunja, Pavlovic, Anto, Hartmann, Felix J, Schreiner, Bettina, Utz, Sebastian G, Leung, Brian P, Lelios, Iva, Heppner, Frank L, Kipnis, Jonathan, Merkler, Doron, Greter, Melanie, Becher, Burkhard
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 20.02.2018
Schlagworte:
high-dimensional
macrophages
experimental autoimmune encephalomyelitis
Alzheimer’s disease
multiple sclerosis
neurodegeneration
aging
mass cytometry
microglia
central nervous system
ISSN:1097-4180, 1097-4180
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Zusammenfassung: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.
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ISSN:1097-4180
1097-4180
DOI:10.1016/j.immuni.2018.01.011