IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-018-05095-7.html
   My bibliography  Save this article

Altered thymic differentiation and modulation of arthritis by invariant NKT cells expressing mutant ZAP70

Author

Listed:
  • Meng Zhao

    (La Jolla Institute for Allergy and Immunology)

  • Mattias N. D. Svensson

    (La Jolla Institute for Allergy and Immunology
    University of California, San Diego)

  • Koen Venken

    (Ghent University
    Ghent University)

  • Ashu Chawla

    (La Jolla Institute for Allergy and Immunology)

  • Shu Liang

    (La Jolla Institute for Allergy and Immunology)

  • Isaac Engel

    (La Jolla Institute for Allergy and Immunology)

  • Piotr Mydel

    (University of Bergen
    Jagiellonian University)

  • Jeremy Day

    (La Jolla Institute for Allergy & Immunology)

  • Dirk Elewaut

    (Ghent University
    Ghent University)

  • Nunzio Bottini

    (La Jolla Institute for Allergy and Immunology
    University of California, San Diego)

  • Mitchell Kronenberg

    (La Jolla Institute for Allergy and Immunology
    University of California San Diego)

Abstract

Various subsets of invariant natural killer T (iNKT) cells with different cytokine productions develop in the mouse thymus, but the factors driving their differentiation remain unclear. Here we show that hypomorphic alleles of Zap70 or chemical inhibition of Zap70 catalysis leads to an increase of IFN-γ-producing iNKT cells (NKT1 cells), suggesting that NKT1 cells may require a lower TCR signal threshold. Zap70 mutant mice develop IL-17-dependent arthritis. In a mouse experimental arthritis model, NKT17 cells are increased as the disease progresses, while NKT1 numbers negatively correlates with disease severity, with this protective effect of NKT1 linked to their IFN-γ expression. NKT1 cells are also present in the synovial fluid of arthritis patients. Our data therefore suggest that TCR signal strength during thymic differentiation may influence not only IFN-γ production, but also the protective function of iNKT cells in arthritis.

Suggested Citation

  • Meng Zhao & Mattias N. D. Svensson & Koen Venken & Ashu Chawla & Shu Liang & Isaac Engel & Piotr Mydel & Jeremy Day & Dirk Elewaut & Nunzio Bottini & Mitchell Kronenberg, 2018. "Altered thymic differentiation and modulation of arthritis by invariant NKT cells expressing mutant ZAP70," Nature Communications, Nature, vol. 9(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05095-7
    DOI: 10.1038/s41467-018-05095-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-05095-7
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-018-05095-7?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. Ludivine Amable & Luis Antonio Ferreira Martins & Remi Pierre & Marcio Cruseiro & Ghita Chabab & Arnauld Sergé & Camille Kergaravat & Marc Delord & Christophe Viret & Jean Jaubert & Chaohong Liu & Sao, 2023. "Intrinsic factors and CD1d1 but not CD1d2 expression levels control invariant natural killer T cell subset differentiation," Nature Communications, Nature, vol. 14(1), pages 1-16, 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:9:y:2018:i:1:d:10.1038_s41467-018-05095-7. 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.