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Extracellular vesicle-associated cholesterol supports the regenerative functions of macrophages in the brain.
Vanherle, Sam; Guns, Jeroen; Loix, Melanie; Mingneau, Fleur; Dierckx, Tess; Wouters, Flore; Kuipers, Koen; Vangansewinkel, Tim; Wolfs, Esther; Lins, Paula Pincela; Bronckaers, Annelies; Lambrichts, Ivo; Dehairs, Jonas; Swinnen, Johannes V; Verberk, Sanne G S; Haidar, Mansour; Hendriks, Jerome J A; Bogie, Jeroen F J.
Afiliación
  • Vanherle S; Department of Immunology and Infection, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium.
  • Guns J; University MS Center Hasselt, Pelt, Belgium.
  • Loix M; Department of Immunology and Infection, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium.
  • Mingneau F; University MS Center Hasselt, Pelt, Belgium.
  • Dierckx T; Department of Immunology and Infection, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium.
  • Wouters F; University MS Center Hasselt, Pelt, Belgium.
  • Kuipers K; Department of Immunology and Infection, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium.
  • Vangansewinkel T; University MS Center Hasselt, Pelt, Belgium.
  • Wolfs E; Department of Immunology and Infection, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium.
  • Lins PP; University MS Center Hasselt, Pelt, Belgium.
  • Bronckaers A; Department of Immunology and Infection, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium.
  • Lambrichts I; University MS Center Hasselt, Pelt, Belgium.
  • Dehairs J; Department of Immunology and Infection, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium.
  • Swinnen JV; University MS Center Hasselt, Pelt, Belgium.
  • Verberk SGS; Department of Cardio and Organs Systems, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium.
  • Haidar M; VIB, Center for Brain & Disease Research, Laboratory of Neurobiology, University of Leuven, Leuven, Belgium.
  • Hendriks JJA; Department of Cardio and Organs Systems, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium.
  • Bogie JFJ; Department of Cardio and Organs Systems, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium.
J Extracell Vesicles ; 12(12): e12394, 2023 12.
Article en En | MEDLINE | ID: mdl-38124258
ABSTRACT
Macrophages play major roles in the pathophysiology of various neurological disorders, being involved in seemingly opposing processes such as lesion progression and resolution. Yet, the molecular mechanisms that drive their harmful and benign effector functions remain poorly understood. Here, we demonstrate that extracellular vesicles (EVs) secreted by repair-associated macrophages (RAMs) enhance remyelination ex vivo and in vivo by promoting the differentiation of oligodendrocyte precursor cells (OPCs). Guided by lipidomic analysis and applying cholesterol depletion and enrichment strategies, we find that EVs released by RAMs show markedly elevated cholesterol levels and that cholesterol abundance controls their reparative impact on OPC maturation and remyelination. Mechanistically, EV-associated cholesterol was found to promote OPC differentiation predominantly through direct membrane fusion. Collectively, our findings highlight that EVs are essential for cholesterol trafficking in the brain and that changes in cholesterol abundance support the reparative impact of EVs released by macrophages in the brain, potentially having broad implications for therapeutic strategies aimed at promoting repair in neurodegenerative disorders.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vesículas Extracelulares Idioma: En Revista: J Extracell Vesicles Año: 2023 Tipo del documento: Article País de afiliación: Bélgica Pais de publicación: Estados Unidos
Texto completo
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vesículas Extracelulares Idioma: En Revista: J Extracell Vesicles Año: 2023 Tipo del documento: Article País de afiliación: Bélgica Pais de publicación: Estados Unidos