Single-cell mass cytometry reveals distinct populations of brain myeloid cells in mouse neuroinflammation and neurodegeneration models
Open accessAbstract
Neuroinflammation and neurodegeneration may represent two poles of brain pathology. Brain myeloid cells, particularly microglia, play key roles in these conditions. We employed single-cell mass cytometry (CyTOF) to compare myeloid cell populations in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis, the R6/2 model of Huntington's disease (HD) and the mutant superoxide dismutase 1 (mSOD1) model of amyotrophic lateral sclerosis (ALS). We identified three myeloid cell populations exclusive to the CNS and present in each disease model. Blood-derived monocytes comprised five populations and migrated to the brain in EAE, but not in HD and ALS models. Single-cell analysis resolved differences in signaling and cytokine production within similar myeloid populations in EAE compared to HD and ALS models. Moreover, these analyses highlighted α5 integrin on myeloid cells as a potential therapeutic target for neuroinflammation. Together, these findings illustrate how neuropathology may differ between inflammatory and degenerative brain disease.
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Monocyte-derived subpopulations characteristically expressed phenotypes involved in activating TH1 and TH17 cells at disease onset, suggesting these cells play a key role in antigen presentation.
“This was further characterized by mass cytometry demonstrating that monocyte-derived subpopulations characteristically expressed phenotypes involved in activating TH1 and TH17 cells at disease onset [4], suggesting these cells play a key role in antigen presentation.”
From Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function (2022) · cites this paper as [4]
The Results section (page unavailable) identifies monocyte populations D and E as likely activated antigen-presenting cells and reports peripheral monocyte subsets during EAE onset. It does not show those subsets activating TH1 or TH17 cells: it instead suggests that populations G and H arise in response to TH1 and TH17 activation, respectively. (LLM, conf=0.88)
Experimental — accuracy not yet measuredDefinitive evidence of a non-redundant role for monocyte-derived APC in activating autoreactive T cells is lacking.
“As both peripherally-derived and CNS-resident myeloid cells have been implicated in antigen presentation to autoreactive T cells, definitive evidence of a non-redundant role for monocyte-derived APC in activating autoreactive T cells is lacking.”
From Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function (2022) · cites this paper as [4]
The Results section (page unavailable) identifies blood-derived monocyte populations D and E as likely activated APCs, and the Discussion says CNS-resident myeloid-cell activation is required for EAE initiation. Neither passage establishes antigen presentation to autoreactive T cells by both populations or explicitly assesses whether definitive evidence for a non-redundant role of monocyte-derived APCs is lacking. (LLM, conf=0.78)
Experimental — accuracy not yet measuredCAMs clear harmful substances through phagocytosis, antigen presentation, and cytokine production.
“As immune surveillants, CAMs clear harmful substances through phagocytosis, antigen presentation, and cytokine production [364,368,371,372,373,374,375,376]”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [371]
The Results (pages not provided) include meningeal and perivascular macrophages among the CNS-resident myeloid cells studied, report cytokine production in those cell populations, and suggest antigen presentation may be a role for one population. The paper does not establish these functions specifically for CAMs, or show that CAMs clear harmful substances through phagocytosis. (LLM, conf=0.82)
Experimental — accuracy not yet measuredSeveral publications within the last 2 years have employed scRNAseq and mass cytometry of microglia and other CNS immune cells to understand global alterations in immunological gene expression and dynamic changes in immune cell-type abundance as a function of brain anatomy, aging, and neurodegeneration.
“Several publications within the last 2 years have begun to employ scRNAseq and mass cytometry of microglia and other CNS immune cells as ways to understand (i) global alterations in immunological gene expression and (ii) dynamic changes in immune cell-type abundance as a function of brain anatomy, aging, and neurodegeneration (87, 95, 107, 108).”
From The Transcriptional Landscape of Microglial Genes in Aging and Neurodegenerative Disease (2019) · cites this paper as [107]
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- Authors
- Ajami, B., Samusik, N., Wieghofer, P., Ho, P. P., Crotti, A., Bjornson, Z., Prinz, M., Fantl, W. J., Nolan, G. P., & Steinman, L.
- Affiliations
- Stanford Medicine (US)
- University of Freiburg (DE)
- University of California San Diego (US)
- Corresponding author
- Ajami, Bahareh
- Steinman, Lawrence
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2018-03-05
- Volume
- 21
- Issue
- 4
- Pages
- 541-551
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC8629134
- OpenAlex
- W2791954023
- Cited by
- 338
- References
- 64
- Citations by year
- 2026: 18 · 2025: 31 · 2024: 32 · 2023: 31 · 2022: 47 · 2021: 75 · 2020: 51 · 2019: 31 · 2018: 22
- FWCI
- 20.08
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- OPUS (Augsburg University) (submittedVersion)
- Funders
- National Institutes of Health (5r01hl120724-05)
- National Heart, Lung, and Blood Institute (R01 - HL120724)
- National Cancer Institute (R33CA183654, R21CA183660, R33CA183692, R01CA184968)
- National Institute of General Medical Sciences (T32GM007276)
- National Institute of Allergy and Infectious Diseases (U19AI100627, U19AI057229)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (UH2AR067676)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Keywords
- microglia, neuroinflammation, neurodegeneration, multiple sclerosis, experimental autoimmune encephalomyelitis, Huntington's disease, amyotrophic lateral sclerosis, monocyte migration, cytokine production, integrin alpha5, therapeutic target, single-cell mass cytometry
- MeSH terms
- Huntingtin Protein, Superoxide Dismutase-1, CX3C Chemokine Receptor 1, Amyotrophic Lateral Sclerosis, Animals, Brain, Disease Models, Animal, Encephalomyelitis, Autoimmune, Experimental, Huntington Disease, Luminescent Proteins, Mice, Inbred C57BL, Mice, Mutant Strains, Mice, Transgenic, Monocytes, Mutation, Cytokines, Myeloid Cells, Intracellular Signaling Peptides and Proteins, CREB-Binding Protein, Mice, Single-Cell Analysis
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