Publication: The metabolic checkpoint kinase mTOR is essential for IL-15 signaling during the development and activation of NK cells

Published in: Nature Immunology, 2014, 15 (8), pp.749-757. ⟨10.1038/ni.2936⟩

Authors: Antoine Marçais, Julien Cherfils-Vicini, Charlotte Viant, Sophie Degouve, Sébastien Viel, Aurore Fenis, Jessica Rabilloud, Katia Mayol, Armelle Tavares, Jacques Bienvenu, Yann-Gaël Gangloff, Eric Gilson, Eric Vivier, Thierry Walzer

Summary

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 mTORC1 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.

Link to HAL – hal-04831545

Link to DOI – 10.1038/ni.2936