| First Author | Marçais A | Year | 2017 |
| Journal | Elife | Volume | 6 |
| PubMed ID | 28875936 | Mgi Jnum | J:248330 |
| Mgi Id | MGI:5916514 | Doi | 10.7554/eLife.26423 |
| Citation | Marcais A, et al. (2017) High mTOR activity is a hallmark of reactive natural killer cells and amplifies early signaling through activating receptors. Elife 6:e26423 |
| abstractText | NK cell education is the process through which chronic engagement of inhibitory NK cell receptors by self MHC-I molecules preserves cellular responsiveness. The molecular mechanisms responsible for NK cell education remain unclear. Here, we show that mouse NK cell education is associated with a higher basal activity of the mTOR/Akt pathway, commensurate to the number of educating receptors. This higher activity was dependent on the SHP-1 phosphatase and essential for the improved responsiveness of reactive NK cells. Upon stimulation, the mTOR/Akt pathway amplified signaling through activating NK cell receptors by enhancing calcium flux and LFA-1 integrin activation. Pharmacological inhibition of mTOR resulted in a proportional decrease in NK cell reactivity. Reciprocally, acute cytokine stimulation restored reactivity of hyporesponsive NK cells through mTOR activation. These results demonstrate that mTOR acts as a molecular rheostat of NK cell reactivity controlled by educating receptors and uncover how cytokine stimulation overcomes NK cell education. |
