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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Published in:	Immunity (Cambridge, Mass.) Vol. 48; no. 2; p. 380
Main Authors:	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
Language:	English
Published:	United States 20.02.2018
Subjects:	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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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.
AbstractList	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. 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.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.
Author	Leung, Brian P Merkler, Doron Kipnis, Jonathan Utz, Sebastian G Lelios, Iva Pavlovic, Anto Hartmann, Felix J Schreiner, Bettina Mrdjen, Dunja Heppner, Frank L Becher, Burkhard Greter, Melanie
Author_xml	– sequence: 1 givenname: Dunja surname: Mrdjen fullname: Mrdjen, Dunja organization: Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland – sequence: 2 givenname: Anto surname: Pavlovic fullname: Pavlovic, Anto organization: Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland – sequence: 3 givenname: Felix J surname: Hartmann fullname: Hartmann, Felix J organization: Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland – sequence: 4 givenname: Bettina surname: Schreiner fullname: Schreiner, Bettina organization: Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland – sequence: 5 givenname: Sebastian G surname: Utz fullname: Utz, Sebastian G organization: Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland – sequence: 6 givenname: Brian P surname: Leung fullname: Leung, Brian P organization: Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland – sequence: 7 givenname: Iva surname: Lelios fullname: Lelios, Iva organization: Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland – sequence: 8 givenname: Frank L surname: Heppner fullname: Heppner, Frank L organization: Department of Neuropathology, Charité-Universitätsmedizin Berlin, Berlin, Germany – sequence: 9 givenname: Jonathan surname: Kipnis fullname: Kipnis, Jonathan organization: Center for Brain Immunology and Glia, Department of Neuroscience, University of Virginia, Charlottesville, VA, USA – sequence: 10 givenname: Doron surname: Merkler fullname: Merkler, Doron organization: Department of Pathology and Immunology, University of Geneva, and Division of Clinical Pathology, Geneva University Hospital, Geneva, Switzerland – sequence: 11 givenname: Melanie surname: Greter fullname: Greter, Melanie organization: Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland – sequence: 12 givenname: Burkhard surname: Becher fullname: Becher, Burkhard email: becher@immunology.uzh.ch organization: Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland. Electronic address: becher@immunology.uzh.ch
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/29426702$$D View this record in MEDLINE/PubMed
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Keywords	high-dimensional macrophages experimental autoimmune encephalomyelitis Alzheimer’s disease multiple sclerosis neurodegeneration aging mass cytometry microglia central nervous system
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Title	High-Dimensional Single-Cell Mapping of Central Nervous System Immune Cells Reveals Distinct Myeloid Subsets in Health, Aging, and Disease
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