IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v5y2014i1d10.1038_ncomms5539.html
   My bibliography  Save this article

Innate immunodeficiency following genetic ablation of Mcl1 in natural killer cells

Author

Listed:
  • Priyanka Sathe

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Rebecca B. Delconte

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Fernando Souza-Fonseca-Guimaraes

    (QIMR Berghofer Medical Research Institute
    School of Medicine, University of Queensland)

  • Cyril Seillet

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Michael Chopin

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Cassandra J. Vandenberg

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Lucille C. Rankin

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Lisa A. Mielke

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Ingela Vikstrom

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Tatiana B. Kolesnik

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Sandra E. Nicholson

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Eric Vivier

    (Centre d’Immunologie de Marseille-Luminy, INSERM)

  • Mark J. Smyth

    (QIMR Berghofer Medical Research Institute
    School of Medicine, University of Queensland)

  • Stephen L. Nutt

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Stefan P. Glaser

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Andreas Strasser

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Gabrielle T. Belz

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Sebastian Carotta

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Nicholas D. Huntington

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

Abstract

The cytokine IL-15 is required for natural killer (NK) cell homeostasis; however, the intrinsic mechanism governing this requirement remains unexplored. Here we identify the absolute requirement for myeloid cell leukaemia sequence-1 (Mcl1) in the sustained survival of NK cells in vivo. Mcl1 is highly expressed in NK cells and regulated by IL-15 in a dose-dependent manner via STAT5 phosphorylation and subsequent binding to the 3′-UTR of Mcl1. Specific deletion of Mcl1 in NK cells results in the absolute loss of NK cells from all tissues owing to a failure to antagonize pro-apoptotic proteins in the outer mitochondrial membrane. This NK lymphopenia results in mice succumbing to multiorgan melanoma metastases, being permissive to allogeneic transplantation and being resistant to toxic shock following polymicrobial sepsis challenge. These results clearly demonstrate a non-redundant pathway linking IL-15 to Mcl1 in the maintenance of NK cells and innate immune responses in vivo.

Suggested Citation

  • Priyanka Sathe & Rebecca B. Delconte & Fernando Souza-Fonseca-Guimaraes & Cyril Seillet & Michael Chopin & Cassandra J. Vandenberg & Lucille C. Rankin & Lisa A. Mielke & Ingela Vikstrom & Tatiana B. K, 2014. "Innate immunodeficiency following genetic ablation of Mcl1 in natural killer cells," Nature Communications, Nature, vol. 5(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5539
    DOI: 10.1038/ncomms5539
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms5539
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms5539?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. Jun Dai & Shuyu Zheng & Matías M. Falco & Jie Bao & Johanna Eriksson & Sanna Pikkusaari & Sofia Forstén & Jing Jiang & Wenyu Wang & Luping Gao & Fernando Perez-Villatoro & Olli Dufva & Khalid Saeed & , 2024. "Tracing back primed resistance in cancer via sister cells," Nature Communications, Nature, vol. 15(1), pages 1-14, 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:5:y:2014:i:1:d:10.1038_ncomms5539. 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.