Stearoyl-CoA desaturase-1 impairs the reparative properties of macrophages and microglia in the brain

Failure of remyelination underlies the progressive nature of demyelinating diseases such as multiple sclerosis. Macrophages and microglia are crucially involved in the formation and repair of demyelinated lesions. Here we show that myelin uptake temporarily skewed these phagocytes toward a disease-r...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:The Journal of experimental medicine Jg. 217; H. 5
Hauptverfasser: Bogie, Jeroen F J, Grajchen, Elien, Wouters, Elien, Corrales, Aida Garcia, Dierckx, Tess, Vanherle, Sam, Mailleux, Jo, Gervois, Pascal, Wolfs, Esther, Dehairs, Jonas, Van Broeckhoven, Jana, Bowman, Andrew P, Lambrichts, Ivo, Gustafsson, Jan-Åke, Remaley, Alan T, Mulder, Monique, Swinnen, Johannes V, Haidar, Mansour, Ellis, Shane R, Ntambi, James M, Zelcer, Noam, Hendriks, Jerome J A
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 04.05.2020
Schlagworte:
Animals
ATP Binding Cassette Transporter 1 - metabolism
Brain - pathology
Cell Line
Cholesterol - metabolism
Endocytosis
Fatty Acids - metabolism
Foam Cells - metabolism
Humans
Inflammation - pathology
Macrophages - enzymology
Macrophages - metabolism
Macrophages - ultrastructure
Mice
Microglia - enzymology
Microglia - metabolism
Myelin Sheath - metabolism
Phagocytes - pathology
Phagocytes - ultrastructure
Phenotype
Protein Kinase C-delta - metabolism
Stearoyl-CoA Desaturase - deficiency
Stearoyl-CoA Desaturase - metabolism
ISSN:1540-9538, 1540-9538
Online-Zugang:Weitere Angaben
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Failure of remyelination underlies the progressive nature of demyelinating diseases such as multiple sclerosis. Macrophages and microglia are crucially involved in the formation and repair of demyelinated lesions. Here we show that myelin uptake temporarily skewed these phagocytes toward a disease-resolving phenotype, while sustained intracellular accumulation of myelin induced a lesion-promoting phenotype. This phenotypic shift was controlled by stearoyl-CoA desaturase-1 (SCD1), an enzyme responsible for the desaturation of saturated fatty acids. Monounsaturated fatty acids generated by SCD1 reduced the surface abundance of the cholesterol efflux transporter ABCA1, which in turn promoted lipid accumulation and induced an inflammatory phagocyte phenotype. Pharmacological inhibition or phagocyte-specific deficiency of Scd1 accelerated remyelination ex vivo and in vivo. These findings identify SCD1 as a novel therapeutic target to promote remyelination.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1540-9538
1540-9538
DOI:10.1084/jem.20191660