IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-019-11638-3.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-11638-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-019-11638-3?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    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. 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.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11638-3. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.