Journal articles
High mTOR activity is a hallmark of reactive natural killer cells and amplifies early signaling through activating receptors
Abstract : 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.
Cited literature [57 references]
https://hal-amu.archives-ouvertes.fr/hal-01764666
Contributor : Carine Dou Goarin <>
Submitted on : Friday, October 26, 2018 - 9:44:25 AM
Last modification on : Tuesday, September 1, 2020 - 3:21:24 AM
Long-term archiving on: : Sunday, January 27, 2019 - 12:55:03 PM
Contributor : Carine Dou Goarin <>
Submitted on : Friday, October 26, 2018 - 9:44:25 AM
Last modification on : Tuesday, September 1, 2020 - 3:21:24 AM
Long-term archiving on: : Sunday, January 27, 2019 - 12:55:03 PM
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