Endothelial cell-derived oxysterol ablation attenuates experimental autoimmune encephalomyelitis.
Détails
Télécharger: 2023_embr.202255328.pdf (4319.92 [Ko])
Etat: Public
Version: Final published version
Licence: CC BY 4.0
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_89C0C5C31546
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Endothelial cell-derived oxysterol ablation attenuates experimental autoimmune encephalomyelitis.
Périodique
EMBO reports
ISSN
1469-3178 (Electronic)
ISSN-L
1469-221X
Statut éditorial
Publié
Date de publication
06/03/2023
Peer-reviewed
Oui
Volume
24
Numéro
3
Pages
e55328
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Résumé
The vasculature is a key regulator of leukocyte trafficking into the central nervous system (CNS) during inflammatory diseases including multiple sclerosis (MS). However, the impact of endothelial-derived factors on CNS immune responses remains unknown. Bioactive lipids, in particular oxysterols downstream of Cholesterol-25-hydroxylase (Ch25h), promote neuroinflammation but their functions in the CNS are not well-understood. Using floxed-reporter Ch25h knock-in mice, we trace Ch25h expression to CNS endothelial cells (ECs) and myeloid cells and demonstrate that Ch25h ablation specifically from ECs attenuates experimental autoimmune encephalomyelitis (EAE). Mechanistically, inflamed Ch25h-deficient CNS ECs display altered lipid metabolism favoring polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC) expansion, which suppresses encephalitogenic T lymphocyte proliferation. Additionally, endothelial Ch25h-deficiency combined with immature neutrophil mobilization into the blood circulation nearly completely protects mice from EAE. Our findings reveal a central role for CNS endothelial Ch25h in promoting neuroinflammation by inhibiting the expansion of immunosuppressive myeloid cell populations.
Mots-clé
cholesterol-25-hydroxylase, endothelial cells, experimental autoimmune encephalomyelitis, oxysterols, polymorphonuclear myeloid-derived suppressor cells
Pubmed
Web of science
Open Access
Oui
Création de la notice
10/02/2023 11:38
Dernière modification de la notice
08/03/2023 6:46