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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TREM2 is 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.
“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]
The Introduction describes foamy macrophages in MS lesions as myelin-scavenging cells derived from microglia or monocytes, and the results say they resemble anti-inflammatory M2 macrophages. The Discussion says they are *likely* to contribute to resolution of inflammation; it does not establish that they promote resolution as a demonstrated function. The TREM2-expression finding is introduced as the citing authors’ own result, not one attributed to this source. (LLM, conf=0.87)
Experimental — accuracy not yet measuredLesions with foamy microglia exhibited increased cholesterol esters and triacylglycerols, consistent with their lipid-laden phenotype, confirmed by Oil Red O staining.
“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]
The foamy-macrophage phenotype section and Fig. 1 caption (page not provided) report abundant neutral lipids in foamy macrophages in multiple sclerosis lesions, demonstrated by Oil Red O staining. They do not identify those lipids as cholesterol esters or triacylglycerols, or report increased levels of either. The paper also describes the foamy cells as arising from both microglia and infiltrating monocytes, rather than identifying them all as microglia. (LLM, conf=0.87)
Experimental — accuracy not yet measuredLack of classical pro-inflammatory signaling has been previously found in MS lesions by mass cytometry of microglia and matches the lipid-induced lysosomal phenotype described in other diseases.
“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]
The Results section ('Foamy macrophages express antiinflammatory markers') reports that lipid-laden macrophages in MS lesions lacked several pro-inflammatory cytokines, and the Discussion proposes that accumulated myelin lipids contribute to their anti-inflammatory phenotype. This supports a resemblance to a lipid-associated phenotype, but the paper does not describe a lysosomal phenotype in other diseases. The mass-cytometry finding is attached to citation 49, not to this source. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThe molecular profile of foamy microglia may reflect metabolic reprogramming associated with the chronic nature of the lesion.
“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]
The Discussion (page unavailable) reports that foamy macrophages have location-dependent molecular profiles that may reflect lipid degradation and local cues; the Introduction says some originate from microglia. The paper studies active lesions, however, and does not attribute those profiles to metabolic reprogramming associated with chronic lesions. (LLM, conf=0.84)
Experimental — accuracy not yet measuredFoamy microglia/macrophages have also been described as anti-inflammatory or immunosuppressed.
“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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- 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 › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Genetics › 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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