The DOI matches its Crossref record; 48 of the 50 references it cites were found in a registry or an index.
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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Cites
The chemokine system in diverse forms of macrophage activation and polarization
MANTOVANI, A., SICA, A., SOZZANI, S., ALLAVENA, P., VECCHI, A., & LOCATI, M. (2004) · Trends in Immunology · doi:10.1016/j.it.2004.09.015 · Cited by 6,534
Alternative activation of macrophages
Gordon, S. (2003) · Nature Reviews Immunology · doi:10.1038/nri978 · Cited by 6,189
MANTOVANI, A., SOZZANI, S., LOCATI, M., ALLAVENA, P., & SICA, A. (2002) · Trends in Immunology · doi:10.1016/s1471-4906(02)02302-5 · Cited by 5,528
Immunology of multiple sclerosis
Sospedra, M., & Martin, R. (2005) · Annual Review of Immunology · doi:10.1146/annurev.immunol.23.021704.115707 · Cited by 2,149
The many faces of macrophage activation
Mosser, D. M. (2003) · Journal of Leukocyte Biology · doi:10.1189/jlb.0602325 · Cited by 1,902
MYELINATION IN RAT BRAIN: METHOD OF MYELIN ISOLATION1
Norton, W. T., & Poduslo, S. E. (1973) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1973.tb07519.x · Cited by 1,413
Prostaglandins as modulators of immunity
Harris, S. G., Padilla, J., Koumas, L., Ray, D. M., & Phipps, R. P. (2002) · Trends in Immunology · doi:10.1016/s1471-4906(01)02154-8 · Cited by 1,168
Reciprocal regulation of inflammation and lipid metabolism by liver X receptors
Joseph, S. B., Castrillo, A., Laffitte, B. A., Mangelsdorf, D. J., & Tontonoz, P. (2003) · Nature Medicine · doi:10.1038/nm820 · Cited by 1,158
Anti-inflammatory lipid mediators and insights into the resolution of inflammation
Lawrence, T., Willoughby, D. A., & Gilroy, D. W. (2002) · Nature reviews. Immunology · doi:10.1038/nri915 · Cited by 879
Dendritic cells permit immune invasion of the CNS in an animal model of multiple sclerosis
Greter, M., Heppner, F. L., Lemos, M. P., Odermatt, B. M., Goebels, N., Laufer, T., Noelle, R. J., & Becher, B. (2005) · Nature Medicine · doi:10.1038/nm1197 · Cited by 862
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- Chayen J, Bitensky L. Analysis of chemical components of cells and tissues; reactions for lipids. In: Practical histochemistry. Chichester: Wiley; 1991. p. 45.
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Zhou, C., Robertson, J. M., Wu, J. G., Bartkowiak, T., Parker, K., McMahon, J., & Lou, Y. (2011) · American Journal of Nephrology · doi:10.1159/000333004 · Cited by 3
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Vogel, D. Y. S. (2015) · Pure Amsterdam UMC · Cited by 3
Li, L., Shi, Y., Luo, Q., Guo, P., Jin, T., Ru, X., Jiang, Z., Niu, Y., Li, W., Chen, Y., et al. (2026) · CNS Neuroscience & Therapeutics · doi:10.1002/cns.70984 · Cited by 2
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Shafit‐Zagardo, B., Sidoli, S., Goldman, J. E., DuBois, J. C., Corboy, J. R., Strittmatter, S. M., Guzik, H. M., Graff, S., & Nagra, R. M. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.05.05.490697 · Cited by 2
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Koning, N., Ilarregui, J. M., García-Vallejo, J. J., & van Kooyk, Y. (2013) · Springer eBooks · doi:10.1007/978-1-4614-7953-6_4 · Cited by 1
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Lorenz, F., Skotnicki, A. B., & Machaczka, M. (2014) · Acta Haematologica Polonica · doi:10.1016/j.achaem.2014.04.004 · Cited by 1
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Antel, J. P. (2010) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/s0317167100022423 · Cited by 1
Kilpatrick, T. J., Ransohoff, R. M., & Wesselingh, S. L. (2009) · Cambridge University Press eBooks · doi:10.1017/cbo9781139195805.006 · Cited by 1
Bradl, M., & Lassmann, H. (2012) · Oxford University Press eBooks · doi:10.1093/med/9780199794591.003.0061 · Cited by 1
Alvarez‐Cermeño, J. C., Gasalla, T., & Villar, L. C. (2009) · Future Neurology · doi:10.2217/14796708.4.2.149 · Cited by 1
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Kopec, B. M., Ebert, E., Ulapane, K. R., Moral, M. E. G., & Siahaan, T. J. (2025) · Neuromethods · doi:10.1007/978-1-0716-4474-4_12
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Pan, J., Forés-Martos, J., Nouh, C. D., Jensen, T. D., Vallejo, K., Cayrol, R., Ahmadian, S. S., Ashley, E. A., Greicius, M. D., & Cobos, I. (2024) · Figshare · doi:10.6084/m9.figshare.26944584
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Fransson, J. (2019) · theses.fr (ABES) · doi:10.70675/361929ebz66c2z48dbz83a1z8955d8b54716
Wuerch, E. C., Baaklini, C. S., Zhang, P., Mørch, M. T., Che, A., D’Mello, C., Ling, C., & Yong, V. W. (2026) · Neurotherapeutics · doi:10.1016/j.neurot.2026.e00943
Lütje, L., Chen, J. Q. A., Hamann, J., Smolders, J., Huitinga, I., & van den Bosch, A. M. R. (2026) · Acta Neuropathologica · doi:10.1007/s00401-026-03040-3
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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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