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6 mars 2023
- doi: 10.15252/embr.202255328
- issn: 1469-221X
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info:eu-repo/semantics/altIdentifier/doi/10.15252/embr.202255328
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info:eu-repo/semantics/altIdentifier/pmid/36715148
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info:eu-repo/semantics/altIdentifier/eissn/1469-3178
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info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_89C0C5C315464
info:eu-repo/semantics/openAccess , CC BY 4.0 , https://creativecommons.org/licenses/by/4.0/
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Meningo-encephalomyelitis Myelinoclasia Perivenous demyelinationCiter ce document
F. Ruiz et al., « Endothelial cell-derived oxysterol ablation attenuates experimental autoimmune encephalomyelitis. », Serveur académique Lausannois, ID : 10.15252/embr.202255328
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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.