The metabolic checkpoint kinase mTOR is essential for IL-15 signaling during the development and activation of NK cells (Nat Immunol. 2014 Aug;15(8):749-57)

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

 Antoine Marçais, Julien Cherfils-Vicini6, Charlotte Viant, Sophie Degouve, Sébastien Viel, Aurore Fenis, Jessica Rabilloud1, Katia Mayol, Armelle Tavares, Jacques Bienvenu, Yann-Gaël Gangloff, Eric Gilson, Eric Vivier & Thierry Walzer ich

Nature Immunology 15(8): 749-57, Aug, 2014

Speaker：林宗成                                            Date：2015/04/07

Commentator：凌斌 老師                                 Room : 602

Abstract

Previous reports have indicated that IL-15 plays a dual role in natural killer (NK) cell biology. The mechanism of single cytokine regulated NK homeostasis and inflammatory effects remain unknown. In this particular study, the authors found NK cells treated with high doses of IL-15, leading to upregulated mTOR activity and promoted metabolic activity, on the contrary, low doses of IL-15 exclusively induced phosphorylation of transcription factor STAT5. Moreover, metabolic regulation through mTOR during NK cell development associated with proliferation and activation by inflammation or viral infection was essential process. Therefore, mTOR indeed plays a key metabolic checkpoint for the NK cell differentiation and activation. Finally the authors found clinically approved mTOR inhibitors abrogate cytotoxicity of NK cell in both human and mouse by pro-inflammatory cytokines. These results could have broad implications in the design of therapies of mTOR inhibitor.

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