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Versican promotes T helper 17 cytotoxic inflammation and impedes oligodendrocyte precursor cell remyelination

Author

Listed:
  • Samira Ghorbani

    (University of Calgary)

  • Emily Jelinek

    (University of Calgary)

  • Rajiv Jain

    (University of Calgary)

  • Benjamin Buehner

    (University of Calgary)

  • Cenxiao Li

    (University of Calgary)

  • Brian M. Lozinski

    (University of Calgary)

  • Susobhan Sarkar

    (University of Calgary)

  • Deepak K. Kaushik

    (University of Calgary)

  • Yifei Dong

    (University of Calgary)

  • Thomas N. Wight

    (Benaroya Research Institute)

  • Soheila Karimi-Abdolrezaee

    (University of Manitoba)

  • Geert J. Schenk

    (Amsterdam Neuroscience, MS Center Amsterdam)

  • Eva M. Strijbis

    (Neurology, Amsterdam Neuroscience, MS Center Amsterdam)

  • Jeroen Geurts

    (Amsterdam Neuroscience, MS Center Amsterdam)

  • Ping Zhang

    (University of Calgary)

  • Chang-Chun Ling

    (University of Calgary)

  • V. Wee Yong

    (University of Calgary)

Abstract

Remyelination failure in multiple sclerosis (MS) contributes to progression of disability. The deficient repair results from neuroinflammation and deposition of inhibitors including chondroitin sulfate proteoglycans (CSPGs). Which CSPG member is repair-inhibitory or alters local inflammation to exacerbate injury is unknown. Here, we correlate high versican-V1 expression in MS lesions with deficient premyelinating oligodendrocytes, and highlight its selective upregulation amongst CSPG members in experimental autoimmune encephalomyelitis (EAE) lesions modeling MS. In culture, purified versican-V1 inhibits oligodendrocyte precursor cells (OPCs) and promotes T helper 17 (Th17) polarization. Versican-V1-exposed Th17 cells are particularly toxic to OPCs. In NG2CreER:MAPTmGFP mice illuminating newly formed GFP+ oligodendrocytes/myelin, difluorosamine (peracetylated,4,4-difluoro-N-acetylglucosamine) treatment from peak EAE reduces lesional versican-V1 and Th17 frequency, while enhancing GFP+ profiles. We suggest that lesion-elevated versican-V1 directly impedes OPCs while it indirectly inhibits remyelination through elevating local Th17 cytotoxic neuroinflammation. We propose CSPG-lowering drugs as potential dual pronged repair and immunomodulatory therapeutics for MS.

Suggested Citation

  • Samira Ghorbani & Emily Jelinek & Rajiv Jain & Benjamin Buehner & Cenxiao Li & Brian M. Lozinski & Susobhan Sarkar & Deepak K. Kaushik & Yifei Dong & Thomas N. Wight & Soheila Karimi-Abdolrezaee & Gee, 2022. "Versican promotes T helper 17 cytotoxic inflammation and impedes oligodendrocyte precursor cell remyelination," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30032-0
    DOI: 10.1038/s41467-022-30032-0
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    References listed on IDEAS

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