Journal
NATURE IMMUNOLOGY
Volume 15, Issue 8, Pages 749-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.2936
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Funding
- FINOVI foundation
- Agence Nationale de la Recherche
- European Research Council [ERC-Stg 281025]
- Institut National de la Sante et de la Recherche Medicale
- Centre National de la Recherche Scientifique
- Universit Claude Bernard Lyon1
- Ecole Normale Superieure de Lyon
- Ligue contre le Cancer
- Aix-Marseille University
- CG06
- INSERM
- FEDER
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Interleukin 15 (IL-15) controls both the homeostasis and the peripheral activation of natural killer (NK) cells. The molecular basis for this duality of action remains unknown. Here we found that the metabolic checkpoint kinase mTOR was activated and boosted bioenergetic metabolism after exposure of NK cells to high concentrations of IL-15, whereas low doses of IL-15 triggered only phosphorylation of the transcription factor STAT5. mTOR stimulated the growth and nutrient uptake of NK cells and positively fed back on the receptor for IL-15. This process was essential for sustaining NK cell proliferation during development and the acquisition of cytolytic potential during inflammation or viral infection. The mTORC 1 inhibitor rapamycin inhibited NK cell cytotoxicity both in mice and humans; this probably contributes to the immunosuppressive activity of this drug in different clinical settings.
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