PXD056856

PXD056856 is an original dataset announced via ProteomeXchange.

Title	Foamy microglia link oxylipins to disease progression in multiple sclerosis
Description	Multiple sclerosis (MS) is a neuroinflammatory disease characterized by expanding demyelinating lesions, leading to severe and irreversible disability.1–4 The mechanisms driving lesion expansion, however, remain poorly understood.5 Here, using a multi-omics approach, we identified foamy microglia lesions as primary contributors to lesion variability and disease progression in secondary progressive MS. Lesions with foamy microglia are marked by the accumulation of cholesterol esters, bismonoacylglycerolphosphates (BMP), and oxylipins, along with increased levels of Immunoglobulin G1, B-cell infiltration, and elevated expression of Fc- and complement receptors. Foamy GPNMB+-microglia display markers of enhanced phagocytosis, lipid metabolism, lysosomal dysfunction, and antigen presentation, but unexpectedly lack classical pro-inflammatory markers. Our data suggest that sustained phagocytosis of myelin overwhelms microglial endo-lysosomal capacity, leading to lipid droplet and oxylipin formation. This stressed microglial phenotype may in turn lead to the recruitment of adaptive immune cells, induce axonal damage, drive lesion expansion and prevent remyelination. Monoacylglycerol lipase, an enzyme producing oxylipin precursors, was identified as a potential therapeutic target to disrupt this cycle and prevent chronic lesion expansion.
HostingRepository	PRIDE
AnnounceDate	2026-09-07
AnnouncementXML	Submission_2026-09-06_19:09:59.535.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tatiana Shamorkina
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-16 06:56:58	ID requested
⏵ 1	2026-09-06 19:10:01	announced

van der Vliet D, Di X, Shamorkina TM, Coulon-Bainier C, Pavlovic A, van der Vliet IACM, Zeng Y, Macnair W, van Egmond N, Chen JQA, van den Bosch AMR, Engelenburg HJ, Wever D, Mason MRJ, Driever WPF, Gagestein B, Dusseldorp E, van Eijk M, Grether U, Harms AC, Hankemeier T, Collin L, Heck AJR, Huitinga I, van der Stelt M, van den Bosch AMR, de Goeij M, Rozemuller AJM, Foamy microglia link oxylipins to disease progression in multiple sclerosis. Nat Neurosci, 29(7):1585-1598(2026) [pubmed]

10.1038/s41593-026-02302-3;

submitter keyword: multiomics, human brain proteomics,MS, Multiple sclerosis

Albert JR Heck
contact affiliation	3Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Padualaan 8, Utrecht 3584 CH, The Netherlands. 4Netherlands Proteomics Center, Padualaan 8, Utrecht 3584 CH, The Netherlands.
contact email	a.j.r.heck@uu.nl
lab head
Tatiana Shamorkina
contact affiliation	Utrecht University
contact email	t.m.shamorkina@uu.nl
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/09/PXD056856

PRIDE project URI

• PRIDE
  1. PXD056856
     1. Label: PRIDE project
     2. Name: Foamy microglia link oxylipins to disease progression in multiple sclerosis