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Endothelial cell-derived oxysterol ablation attenuates experimental autoimmune encephalomyelitis.

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  • معلومة اضافية
    • Contributors:
      UCL - SSS/LDRI - Louvain Drug Research Institute
    • بيانات النشر:
      Wiley Blackwell
    • الموضوع:
      2023
    • Collection:
      DIAL@UCL (Université catholique de Louvain)
    • نبذة مختصرة :
      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 TÂ 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.
    • ISSN:
      1469-221X
      1469-3178
    • Relation:
      boreal:276326; http://hdl.handle.net/2078.1/276326; info:pmid/36715148; urn:ISSN:1469-221X; urn:EISSN:1469-3178
    • الرقم المعرف:
      10.15252/embr.202255328
    • الدخول الالكتروني :
      http://hdl.handle.net/2078.1/276326
      https://doi.org/10.15252/embr.202255328
    • Rights:
      info:eu-repo/semantics/openAccess
    • الرقم المعرف:
      edsbas.85281E21