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Myelin-laden macrophages are anti-inflammatory, consistent with foam cells in multiple sclerosis
Abstract
Multiple sclerosis lesion activity concurs with the extent of inflammation, demyelination and axonal suffering. Pro-inflammatory myeloid cells contribute to lesion development, but the self-limiting nature of lesions implies as yet unidentified anti-inflammatory mechanisms. We addressed the hypothesis that myelin ingestion by myeloid cells induces a foamy appearance and confers anti-inflammatory function. First, we show that myelin-containing foam cells in multiple sclerosis lesions consistently express a series of anti-inflammatory molecules while lacking pro-inflammatory cytokines. Second, unique location-dependent cytokine and membrane receptor expression profiles imply functional specialization allowing for differential responses to micro-environmental cues. A novel human in vitro model of foamy macrophages functionally confirmed that myelin ingestion induces an anti-inflammatory programme. Foamy macrophages are unable to respond to prototypical inflammatory stimuli but do express molecules involved in suppression of inflammation. These findings provide novel insights into the mechanisms of lesion control and may open new roads to intervention.
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“Here we show that TREM2 was highly expressed within active MS lesions by lipid-laden microglia/macrophages known to display an alternatively activated M2 profile and to promote the resolution of inflammation and clearance of myelin debris [5].”
From TREM2 activation on microglia promotes myelin debris clearance and remyelination in a model of multiple sclerosis (2020) · cites this paper as [5]
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“Lesions with foamy microglia exhibited increased cholesterol esters (CEs) and triacylglycerols (TAG), consistent with their lipid-laden phenotype, which was confirmed by the neutral lipid staining Oil Red O (ORO)14,16”
From Foamy microglia link oxylipins to disease progression in multiple sclerosis (2026) · cites this paper as [14]
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“This lack of classical pro-inflammatory signaling has been previously found in MS lesions by mass cytometry of microglia49 and matches the lipid-induced lysosomal phenotype described in other diseases14,18,50,51.”
From Foamy microglia link oxylipins to disease progression in multiple sclerosis (2026) · cites this paper as [14]
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“which may potentially reflect metabolic reprogramming associated with the chronic nature of the lesion14,18,50.”
From Foamy microglia link oxylipins to disease progression in multiple sclerosis (2026) · cites this paper as [14]
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“However, foamy microglia/macrophages have also been described as anti-inflammatory or immunosuppressed14,18.”
From Foamy microglia link oxylipins to disease progression in multiple sclerosis (2026) · cites this paper as [14]
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“lipid-laden microglia/macrophages are immunosuppressive (20)”
From Reduced Angiopoietin-Like 4 Expression in Multiple Sclerosis Lesions Facilitates Lipid Uptake by Phagocytes via Modulation of Lipoprotein-Lipase Activity (2019) · cites this paper as [20]
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Metadata
- Authors
- Boven, L. A., Van Meurs, M., Van Zwam, M., Wierenga-Wolf, A., Hintzen, R. Q., Boot, R. G., Aerts, J. M., Amor, S., Nieuwenhuis, E. E., & Laman, J. D.
- Affiliations
- Erasmus MC (NL)
- Amsterdam UMC Location University of Amsterdam (NL)
- Biomedical Primate Research Centre (NL)
- Corresponding author
- Boven, Leonie A.
- ORCID
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-12-19
- Volume
- 129
- Issue
- 2
- Pages
- 517-526
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W2166298859
- Cited by
- 353
- References
- 50
- Citations by year
- 2026: 10 · 2025: 14 · 2024: 19 · 2023: 13 · 2022: 17 · 2021: 26 · 2020: 20 · 2019: 21 · 2018: 25 · 2017: 13 · 2016: 21 · 2015: 29 · 2014: 28 · 2013: 17 · 2012: 11
- FWCI
- 6.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Keywords
- multiple sclerosis, foam cells, anti-inflammatory macrophages, myeloid cells, demyelination, cytokine expression, cell surface receptors, in vitro macrophage model, neuroinflammation
- MeSH terms
- Brain, Cells, Cultured, Enzyme-Linked Immunosorbent Assay, Humans, Immunohistochemistry, Macrophages, Myelin Sheath, RNA, Messenger, Sialoglycoproteins, Biomarkers, Interleukin-4, Transforming Growth Factor beta, Interleukin-10, Chemokines, CC, Reverse Transcriptase Polymerase Chain Reaction, Multiple Sclerosis, Relapsing-Remitting, Interleukin 1 Receptor Antagonist Protein
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