Endothelial cell‐derived oxysterol ablation attenuates experimental autoimmune encephalomyelitis

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.

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch

References and Relationships

• Bibliographic citation: Endothelial cell‐derived oxysterol ablation attenuates experimental autoimmune encephalomyelitis ; day:30 ; month:01 ; year:2023 ; extent:20 ; EMBO reports / European Molecular Biology Organization ; (30.01.2023) (gesamt 20)

Contributors, Places and Time

• Creator: Ruiz, Florian ; Peter, Benjamin ; Rebeaud, Jessica ; Vigne, Solenne ; Bressoud, Valentine ; Roumain, Martin ; Wyss, Tania ; Yersin, Yannick ; Wagner, Ingrid ; Kreutzfeldt, Mario ; Pimentel Mendes, Marisa ; Kowalski, Camille ; Boivin, Gael ; Roth, Leonard ; Schwaninger, Markus ; Merkler, Doron ; Muccioli, Giulio G. ; Hugues, Stephanie ; Petrova, Tatiana V. ; Pot, Caroline

Further information

• DOI: 10.15252/embr.202255328
• URN: urn:nbn:de:101:1-2023013014115974012990
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 15.08.2025, 7:24 AM CEST