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

被引：483

作者：

Marais, Antoine ^{[1
,2
,3
,4
,5
]}

Cherfils-Vicini, Julien ^{[6
]}

Viant, Charlotte ^{[7
]}

Degouve, Sophie ^{[1
,2
,3
,4
,5
]}

Viel, Sebastien ^{[1
,2
,3
,4
,5
,8
]}

Fenis, Aurore ^{[7
]}

Rabilloud, Jessica ^{[1
,2
,3
,4
,5
]}

Mayol, Katia ^{[1
,2
,3
,4
,5
]}

Tavares, Armelle ^{[1
,2
,3
,4
,5
]}

Bienvenu, Jacques ^{[8
]}

Gangloff, Yann-Gael ^{[3
,9
]}

Gilson, Eric ^{[6
,10
]}

Vivier, Eric ^{[7
]}

Walzer, Thierry ^{[1
,2
,3
,4
,5
]}

机构：

[1] Int Ctr Infectiol Res, Lyon, France

[2] INSERM, U1111, F-69008 Lyon, France

[3] Ecole Normale Super Lyon, F-69364 Lyon, France

[4] Univ Lyon 1, F-69365 Lyon, France

[5] CNRS, UMR5308, Lyon, France

[6] Univ Nice, Fac Med, CNRS INSERM UMR7284 U1081, Inst Res Canc & Aging, Nice, France

[7] Aix Marseille Univ, UM2, CNRS UMR7280, Ctr Immunol Marseille Luminy,INSERM U1104, Marseille, France

[8] Ctr Hosp Lyon Sud, Hosp Civils Lyon, Immunol Lab, Lyon, France

[9] CNRS, UMR 5239, Lab Biol Mol & Cellulaire, Lyon, France

[10] CHU Nice, Archet Hosp 2, Dept Med Genet, F-06202 Nice, France

来源：

NATURE IMMUNOLOGY | 2014年 / 15卷 / 08期

基金：

欧洲研究理事会;

关键词：

ROR-GAMMA-T; NATURAL-KILLER; MAMMALIAN TARGET; LYMPHOID-CELLS; MATURATION; PATHWAYS; EFFECTOR; PHOSPHORYLATION; DIFFERENTIATION; P110-DELTA;

D O I：

10.1038/ni.2936

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：749 / +

页数：10

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