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Science ; 363(6425)2019 01 25.
Article in English | MEDLINE | ID: mdl-30679343

ABSTRACT

The innate immune cell compartment is highly diverse in the healthy central nervous system (CNS), including parenchymal and non-parenchymal macrophages. However, this complexity is increased in inflammatory settings by the recruitment of circulating myeloid cells. It is unclear which disease-specific myeloid subsets exist and what their transcriptional profiles and dynamics during CNS pathology are. Combining deep single-cell transcriptome analysis, fate mapping, in vivo imaging, clonal analysis, and transgenic mouse lines, we comprehensively characterized unappreciated myeloid subsets in several CNS compartments during neuroinflammation. During inflammation, CNS macrophage subsets undergo self-renewal, and random proliferation shifts toward clonal expansion. Last, functional studies demonstrated that endogenous CNS tissue macrophages are redundant for antigen presentation. Our results highlight myeloid cell diversity and provide insights into the brain's innate immune system.


Subject(s)
Central Nervous System/immunology , Immunity, Innate , Inflammation/immunology , Macrophages/cytology , Myeloid Cells/cytology , Animals , Antigen Presentation , Brain/immunology , Dendritic Cells/cytology , Encephalomyelitis, Autoimmune, Experimental/immunology , Histocompatibility Antigens Class II/immunology , Homeostasis , Macrophages/immunology , Mice, Inbred C57BL , Mice, Transgenic , Monocytes/cytology , Myeloid Cells/immunology , Sequence Analysis, RNA , Single-Cell Analysis , T-Lymphocytes/immunology
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