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

被引：563

作者：

Mrdjen, Dunja ^{[1
]}

Pavlovic, Anto ^{[1
]}

Hartmann, Felix J. ^{[1
]}

Schreiner, Bettina ^{[1
]}

Utz, Sebastian G. ^{[1
]}

Leung, Brian P. ^{[1
]}

Lelios, Iva ^{[1
]}

Heppner, Frank L. ^{[2
]}

Kipnis, Jonathan ^{[3
]}

Merkler, Doron ^{[4
,5
]}

Greter, Melanie ^{[1
]}

Becher, Burkhard ^{[1
]}

机构：

[1] Univ Zurich, Inst Expt Immunol, Zurich, Switzerland

[2] Charite Univ Med Berlin, Dept Neuropathol, Berlin, Germany

[3] Univ Virginia, Ctr Brain Immunol & Glia, Dept Neurosci, Charlottesville, VA USA

[4] Univ Geneva, Dept Pathol & Immunol, Geneva, Switzerland

[5] Geneva Univ Hosp, Div Clin Pathol, Geneva, Switzerland

来源：

IMMUNITY | 2018年 / 48卷 / 02期

基金：

瑞士国家科学基金会; 美国国家科学基金会;

关键词：

DENDRITIC CELLS; GM-CSF; MASS CYTOMETRY; CHOROID-PLEXUS; T-CELLS; MICROGLIA; INFLAMMATION; MACROPHAGES; MONOCYTES; PATHOLOGY;

D O I：

10.1016/j.immuni.2018.01.011

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：380 / +

页数：22

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