Peer-reviewedCC BYNature Neuroscience
Foamy microglia link oxylipins to disease progression in multiple sclerosis
14 affiliations
- 1Department of Molecular Physiology, Leiden Institute of Chemistry, Leiden University, Leiden, the Netherlands
- 2Neuroimmunology Research Group, Netherlands Institute for Neuroscience, Amsterdam, the Netherlands
- 3Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Utrecht, the Netherlands
- 4Netherlands Proteomics Center, Utrecht, the Netherlands
- 5Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche, Basel, Switzerland
- 6Methodology and Statistics Unit, Institute of Psychology, Leiden University, Leiden, the Netherlands
- 7Department of Bio-organic Synthesis, Leiden Institute of Chemistry, Leiden University, Leiden, the Netherlands
- 8The Netherlands Brain Bank, Netherlands Institute for Neuroscience, Amsterdam, the Netherlands
- 9Department of Pathology, Amsterdam University Medical Centre, Amsterdam, the Netherlands
- 10Metabolomics and Analytics Centre, Leiden Academic Centre for Drug Research, Leiden University, Leiden, the Netherlands
- 11Center for Neuroscience, Swammerdam Institute for Life Sciences, Faculty of Science, University of Amsterdam, Amsterdam, the Netherlands. [email protected]
- 12Neuroimmunology Research Group, Netherlands Institute for Neuroscience, Amsterdam, the Netherlands. [email protected]
- 13The Netherlands Brain Bank, Netherlands Institute for Neuroscience, Amsterdam, the Netherlands. [email protected]
- 14Department of Molecular Physiology, Leiden Institute of Chemistry, Leiden University, Leiden, the Netherlands. [email protected]
Abstract
microglia/macrophages associated with lesion expansion in secondary progressive MS. Using integrated lipidomic, transcriptomic, proteomic, chemical proteomic and histological analyses of human postmortem MS lesions, we show that lesions containing foamy microglia/macrophages exhibit disrupted lipid metabolism, lysosomal stress and markers associated with heightened phagocytosis and antigen presentation without classical pro-inflammatory signatures. These lesions are enriched for oxylipins, bismonoacylglycerolphosphates and cholesterol esters, and are associated with increased B cell infiltration and IgG1. Monoacylglycerol lipase (MAGL), a lipid-metabolizing enzyme enriched in lesions with foamy microglia/macrophages, emerged as a potential therapeutic target. Inhibition of MAGL promoted lesion recovery and reduced microgliosis in a mouse model of demyelination. Finally, oxylipins in cerebrospinal fluid correlate with the proportion of foamy lesions, suggesting potential biomarkers for progression. Our findings implicate disturbed lipid metabolism in chronic MS pathology and suggest that foamy microglia/macrophages are an interesting cell type to target for progressive disease.
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BibTeX
@article{vliet2026foamy,
title = {{Foamy microglia link oxylipins to disease progression in multiple sclerosis}},
author = {Daan van der Vliet and Xinyu Di and Tatiana M. Shamorkina and Claire Coulon-Bainier and Anto Pavlovic and Iris A. C. M. van der Vliet and Yingyu Zeng and Will Macnair and Noëlle van Egmond and J.Q. Alida Chen and Aletta M. R. van den Bosch and Hendrik J. Engelenburg and Dennis Wever and Matthew R. J. Mason and Wouter P. F. Driever and Berend Gagestein and Elise Dusseldorp and Marco van Eijk and Uwe Grether and The Netherlands Brain Bank and Aletta M. R. van den Bosch and Mignon de Goeij and Annemieke J.M. Rozemüller and Amy C. Harms and Thomas Hankemeier and Ludovic Collin and Albert J. R. Heck and Inge Huitinga and Mario van der Stelt},
journal = {Nature Neuroscience},
year = {2026},
month = may,
doi = {10.1038/s41593-026-02302-3},
url = {https://doi.org/10.1038/s41593-026-02302-3},
note = {CC BY},
}
RIS
TY - JOUR
TI - Foamy microglia link oxylipins to disease progression in multiple sclerosis
AU - Daan van der Vliet
AU - Xinyu Di
AU - Tatiana M. Shamorkina
AU - Claire Coulon-Bainier
AU - Anto Pavlovic
AU - Iris A. C. M. van der Vliet
AU - Yingyu Zeng
AU - Will Macnair
AU - Noëlle van Egmond
AU - J.Q. Alida Chen
AU - Aletta M. R. van den Bosch
AU - Hendrik J. Engelenburg
AU - Dennis Wever
AU - Matthew R. J. Mason
AU - Wouter P. F. Driever
AU - Berend Gagestein
AU - Elise Dusseldorp
AU - Marco van Eijk
AU - Uwe Grether
AU - The Netherlands Brain Bank
AU - Aletta M. R. van den Bosch
AU - Mignon de Goeij
AU - Annemieke J.M. Rozemüller
AU - Amy C. Harms
AU - Thomas Hankemeier
AU - Ludovic Collin
AU - Albert J. R. Heck
AU - Inge Huitinga
AU - Mario van der Stelt
PY - 2026
DA - 2026/05/21
JO - Nature Neuroscience
DO - 10.1038/s41593-026-02302-3
UR - https://doi.org/10.1038/s41593-026-02302-3
AB - microglia/macrophages associated with lesion expansion in secondary progressive MS. Using integrated lipidomic, transcriptomic, proteomic, chemical proteomic and histological analyses of human postmortem MS lesions, we show that lesions containing foamy microglia/macrophages exhibit disrupted lipid metabolism, lysosomal stress and markers associated with heightened phagocytosis and antigen presentation without classical pro-inflammatory signatures. These lesions are enriched for oxylipins, bismonoacylglycerolphosphates and cholesterol esters, and are associated with increased B cell infiltration and IgG1. Monoacylglycerol lipase (MAGL), a lipid-metabolizing enzyme enriched in lesions with foamy microglia/macrophages, emerged as a potential therapeutic target. Inhibition of MAGL promoted lesion recovery and reduced microgliosis in a mouse model of demyelination. Finally, oxylipins in cerebrospinal fluid correlate with the proportion of foamy lesions, suggesting potential biomarkers for progression. Our findings implicate disturbed lipid metabolism in chronic MS pathology and suggest that foamy microglia/macrophages are an interesting cell type to target for progressive disease.
SN - 1097-6256
SN - 1546-1726
ER -