Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Nat Immunol. 2007 Aug;8(8):856-63. Epub 2007 Jul 8.

Interleukin 15-mediated survival of natural killer cells is determined by interactions among Bim, Noxa and Mcl-1.

Author information

  • 1The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia. nhunting@pasteur.fr

Abstract

Interleukin 15 (IL-15) promotes the survival of natural killer (NK) cells by preventing apoptosis through mechanisms unknown at present. Here we identify Bim, Noxa and Mcl-1 as key regulators of IL-15-dependent survival of NK cells. IL-15 suppressed apoptosis by limiting Bim expression through the kinases Erk1 and Erk2 and mechanisms dependent on the transcription factor Foxo3a, while promoting expression of Mcl-1, which was necessary and sufficient for the survival of NK cells. Withdrawal of IL-15 led to upregulation of Bim and, accordingly, both Bim-deficient and Foxo3a-/- NK cells were resistant to cytokine deprivation. Finally, IL-15-mediated inactivation of Foxo3a and cell survival were dependent on phosphotidylinositol-3-OH kinase. Thus, IL-15 regulates the survival of NK cells at multiple steps, with Bim and Noxa being key antagonists of Mcl-1, the critical survivor factor in this process.

PMID:
17618288
[PubMed - indexed for MEDLINE]
PMCID:
PMC2951739
Free PMC Article

Publication Types, MeSH Terms, Substances, Grant Support

Publication Types

MeSH Terms

Substances

Grant Support

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Write to the Help Desk