Canonical TGF-β signaling pathway represses human NK cell metabolism

V Zaiatz-Bittencourt, DK Finlay… - The Journal of …, 2018 - journals.aai.org
The Journal of Immunology, 2018journals.aai.org
Cytokines stimulate rapid metabolic changes in human NK cells, including increases in both
glycolysis and oxidative phosphorylation pathways. However, how these are subsequently
regulated is not known. In this study, we demonstrate that TGF-β can inhibit many of these
metabolic changes, including oxidative phosphorylation, glycolytic capacity, and respiratory
capacity. TGF-β also inhibited cytokine-induced expression of the transferrin nutrient
receptor CD71. In contrast to a recent report on murine NK cells, TGF-β–mediated …
Abstract
Cytokines stimulate rapid metabolic changes in human NK cells, including increases in both glycolysis and oxidative phosphorylation pathways. However, how these are subsequently regulated is not known. In this study, we demonstrate that TGF-β can inhibit many of these metabolic changes, including oxidative phosphorylation, glycolytic capacity, and respiratory capacity. TGF-β also inhibited cytokine-induced expression of the transferrin nutrient receptor CD71. In contrast to a recent report on murine NK cells, TGF-β–mediated suppression of these metabolic responses did not involve the inhibition of the metabolic regulator mTORC1. Inhibition of the canonical TGF-β signaling pathway was able to restore almost all metabolic and functional responses that were inhibited by TGF-β. These data suggest that pharmacological inhibition of TGF-β could provide a metabolic advantage to NK cells that is likely to result in improved functional responses. This has important implications for NK cell–based cancer immunotherapies.
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