دورية أكاديمية
High mTOR activity is a hallmark of reactive natural killer cells and amplifies early signaling through activating receptors
| العنوان: | High mTOR activity is a hallmark of reactive natural killer cells and amplifies early signaling through activating receptors |
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| المؤلفون: | Antoine Marçais, Marie Marotel, Sophie Degouve, Alice Koenig, Sébastien Fauteux-Daniel, Annabelle Drouillard, Heinrich Schlums, Sébastien Viel, Laurie Besson, Omran Allatif, Mathieu Bléry, Eric Vivier, Yenan Bryceson, Olivier Thaunat, Thierry Walzer |
| المصدر: | eLife, Vol 6 (2017) |
| بيانات النشر: | eLife Sciences Publications Ltd, 2017. |
| سنة النشر: | 2017 |
| المجموعة: | LCC:Medicine LCC:Science LCC:Biology (General) |
| مصطلحات موضوعية: | natural killer, cell signaling, mTOR, education, activation threshold, Medicine, Science, Biology (General), QH301-705.5 |
| الوصف: | 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2050-084X |
| العلاقة: | https://elifesciences.org/articles/26423Test; https://doaj.org/toc/2050-084XTest |
| DOI: | 10.7554/eLife.26423 |
| الوصول الحر: | https://doaj.org/article/16b479fd084d4135bef30037b9969ddaTest |
| رقم الانضمام: | edsdoj.16b479fd084d4135bef30037b9969dda |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2050084X |
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| DOI: | 10.7554/eLife.26423 |