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

Autor: Ghorbani S; Hotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, Calgary, Canada., Jelinek E; Hotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, Calgary, Canada., Jain R; Hotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, Calgary, Canada., Buehner B; Hotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, Calgary, Canada., Li C; Hotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, Calgary, Canada., Lozinski BM; Hotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, Calgary, Canada., Sarkar S; Hotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, Calgary, Canada., Kaushik DK; Hotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, Calgary, Canada., Dong Y; Hotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, Calgary, Canada., Wight TN; Benaroya Research Institute, Seattle, United States., Karimi-Abdolrezaee S; Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Canada., Schenk GJ; Department of Anatomy and Neurosciences, Amsterdam Neuroscience, MS Center Amsterdam, Amsterdam, The Netherlands., Strijbis EM; Neurology, Amsterdam Neuroscience, MS Center Amsterdam, Amsterdam, The Netherlands., Geurts J; Department of Anatomy and Neurosciences, Amsterdam Neuroscience, MS Center Amsterdam, Amsterdam, The Netherlands., Zhang P; Department of Chemistry, University of Calgary, Calgary, Canada., Ling CC; Department of Chemistry, University of Calgary, Calgary, Canada., Yong VW; Hotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, Calgary, Canada. vyong@ucalgary.ca.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 May 04; Vol. 13 (1), pp. 2445. Date of Electronic Publication: 2022 May 04.
DOI: 10.1038/s41467-022-30032-0
Abstrakt: 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 NG2 CreER :MAPT mGFP 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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