Endothelial cell-derived oxysterol ablation attenuates experimental autoimmune encephalomyelitis.

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State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_89C0C5C31546
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Endothelial cell-derived oxysterol ablation attenuates experimental autoimmune encephalomyelitis.
Journal
EMBO reports
Author(s)
Ruiz F., Peter B., Rebeaud J., Vigne S., Bressoud V., Roumain M., Wyss T., Yersin Y., Wagner I., Kreutzfeldt M., Pimentel Mendes M., Kowalski C., Boivin G., Roth L., Schwaninger M., Merkler D., Muccioli G.G., Hugues S., Petrova T.V., Pot C.
ISSN
1469-3178 (Electronic)
ISSN-L
1469-221X
Publication state
Published
Issued date
06/03/2023
Peer-reviewed
Oui
Volume
24
Number
3
Pages
e55328
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
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.
Keywords
cholesterol-25-hydroxylase, endothelial cells, experimental autoimmune encephalomyelitis, oxysterols, polymorphonuclear myeloid-derived suppressor cells
Pubmed
Web of science
Open Access
Yes
Create date
10/02/2023 11:38
Last modification date
08/03/2023 6:46
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