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Immunity. 2018 Feb 20;48(2):380-395.e6. doi: 10.1016/j.immuni.2018.01.011. Epub 2018 Feb 6.

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

Author information

1
Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
2
Department of Neuropathology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
3
Center for Brain Immunology and Glia, Department of Neuroscience, University of Virginia, Charlottesville, VA, USA.
4
Department of Pathology and Immunology, University of Geneva, and Division of Clinical Pathology, Geneva University Hospital, Geneva, Switzerland.
5
Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland. Electronic address: becher@immunology.uzh.ch.

Abstract

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.

KEYWORDS:

Alzheimer’s disease; aging; central nervous system; experimental autoimmune encephalomyelitis; high-dimensional; macrophages; mass cytometry; microglia; multiple sclerosis; neurodegeneration

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PMID:
29426702
DOI:
10.1016/j.immuni.2018.01.011
[Indexed for MEDLINE]
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