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Oligodendrocyte precursor cells present antigen and are cytotoxic targets in inflammatory demyelination

Author

Listed:
  • Leslie Kirby

    (Johns Hopkins School of Medicine)

  • Jing Jin

    (Johns Hopkins School of Medicine)

  • Jaime Gonzalez Cardona

    (Johns Hopkins School of Medicine)

  • Matthew D. Smith

    (Johns Hopkins School of Medicine)

  • Kyle A. Martin

    (Johns Hopkins School of Medicine)

  • Jingya Wang

    (MedImmune LLC)

  • Hayley Strasburger

    (Johns Hopkins School of Medicine)

  • Leyla Herbst

    (Johns Hopkins School of Medicine)

  • Maya Alexis

    (Johns Hopkins School of Medicine)

  • Jodi Karnell

    (MedImmune LLC)

  • Todd Davidson

    (MedImmune LLC)

  • Ranjan Dutta

    (Cleveland Clinic Foundation)

  • Joan Goverman

    (University of Washington)

  • Dwight Bergles

    (Johns Hopkins School of Medicine)

  • Peter A. Calabresi

    (Johns Hopkins School of Medicine
    Johns Hopkins School of Medicine)

Abstract

Oligodendrocyte precursor cells (OPCs) are abundant in the adult central nervous system, and have the capacity to regenerate oligodendrocytes and myelin. However, in inflammatory diseases such as multiple sclerosis (MS) remyelination is often incomplete. To investigate how neuroinflammation influences OPCs, we perform in vivo fate-tracing in an inflammatory demyelinating mouse model. Here we report that OPC differentiation is inhibited by both effector T cells and IFNγ overexpression by astrocytes. IFNγ also reduces the absolute number of OPCs and alters remaining OPCs by inducing the immunoproteasome and MHC class I. In vitro, OPCs exposed to IFNγ cross-present antigen to cytotoxic CD8 T cells, resulting in OPC death. In human demyelinated MS brain lesions, but not normal appearing white matter, oligodendroglia exhibit enhanced expression of the immunoproteasome subunit PSMB8. Therefore, OPCs may be co-opted by the immune system in MS to perpetuate the autoimmune response, suggesting that inhibiting immune activation of OPCs may facilitate remyelination.

Suggested Citation

  • Leslie Kirby & Jing Jin & Jaime Gonzalez Cardona & Matthew D. Smith & Kyle A. Martin & Jingya Wang & Hayley Strasburger & Leyla Herbst & Maya Alexis & Jodi Karnell & Todd Davidson & Ranjan Dutta & Joa, 2019. "Oligodendrocyte precursor cells present antigen and are cytotoxic targets in inflammatory demyelination," Nature Communications, Nature, vol. 10(1), pages 1-20, December.
  • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11638-3
    DOI: 10.1038/s41467-019-11638-3
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    Cited by:

    1. Thaddeus J. Kunkel & Alice Townsend & Kyle A. Sullivan & Jean Merlet & Edward H. Schuchman & Daniel A. Jacobson & Andrew P. Lieberman, 2023. "The cholesterol transporter NPC1 is essential for epigenetic regulation and maturation of oligodendrocyte lineage cells," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Tian Zhou & Yuxin Li & Xiaoyu Li & Fanzhuo Zeng & Yanxia Rao & Yang He & Yafei Wang & Meizhen Liu & Dali Li & Zhen Xu & Xin Zhou & Siling Du & Fugui Niu & Jiyun Peng & Xifan Mei & Sheng-Jian Ji & Yous, 2022. "Microglial debris is cleared by astrocytes via C4b-facilitated phagocytosis and degraded via RUBICON-dependent noncanonical autophagy in mice," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    3. Jean-Baptiste Huré & Louis Foucault & Litsa Maria Ghayad & Corentine Marie & Nicolas Vachoud & Lucas Baudouin & Rihab Azmani & Natalija Ivjanin & Alvaro Arevalo-Nuevo & Morgane Pigache & Lamia Bouslam, 2024. "Pharmacogenomic screening identifies and repurposes leucovorin and dyclonine as pro-oligodendrogenic compounds in brain repair," Nature Communications, Nature, vol. 15(1), pages 1-24, December.
    4. Jing-Ping Lin & Hannah M. Kelly & Yeajin Song & Riki Kawaguchi & Daniel H. Geschwind & Steven Jacobson & Daniel S. Reich, 2022. "Transcriptomic architecture of nuclei in the marmoset CNS," Nature Communications, Nature, vol. 13(1), pages 1-21, December.

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