Metabolic Reprogramming Supports IFN-γ Production by CD56bright NK Cells

• DOI: 10.4049/jimmunol.1501783
• Publication Date: 2016-02-13T12:18:41Z
• Authors: Sinéad E Keating; Vanessa Zaiatz-Bi...; Roisín M Loftus; Ciara Keane; Kiva Brennan; David K Finlay; Clair M Gardiner
• Keywords: Reprogramming

Abstract Human NK cells can be classified into phenotypically and functionally distinct subsets based on levels of CD56 receptor. CD56dim are generally considered more cytotoxic, whereas the CD56bright potent producers IFN-γ. In this study, we define metabolic changes that occur in peripheral blood response to cytokine. Metabolic analysis showed upregulate glycolysis oxidative phosphorylation either IL-2 or IL-12/15 cytokine combinations. Despite fact both these combinations robustly upregulated mammalian Target Rapamycin Complex 1 human cells, only IL-2–induced were sensitive inhibition by rapamycin. Interestingly, found metabolically active compared with cells. They preferentially nutrient receptors also differed substantially terms their glucose metabolism. expressed high uptake receptor, Glut1 (in absence any cytokine), had higher rates Elevated required support cytotoxicity IFN-γ production all Finally, although elevated was not directly for cell degranulation, limiting rate significantly impaired subset Overall, have defined than which supports large amounts during an immune response.