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快乐十分怎么赚钱:Enhanced oxidative phosphorylation in NKT cells is essential for their survival and function
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The role of cellular metabolism in conventional T cell fate and functions has been established, but little is understood about how metabolic pathways and nutrient requirements are controlled in natural killer T (NKT) cells. The present study shows that, unlike CD4 T cells, activation of NKT cells metabolize glucose to the pentose phosphate pathway and TCA cycle instead of converting into lactate. In line with this, a high lactate microenvironment is detrimental for NKT cell homeostasis and effector function. Glucose metabolism and IFN-γ expression is increased in NKT cells in response to bacterial infection. Taking these data together, our study demonstrates unique glucose metabolic regulation necessary for NKT cell survival, proliferation and cytokine expression.
Cellular metabolism and signaling pathways are key regulators to determine conventional T cell fate and function, but little is understood about the role of cell metabolism for natural killer T (NKT) cell survival, proliferation, and function. We found that NKT cells operate distinct metabolic programming from CD4 T cells. NKT cells are less efficient in glucose uptake than CD4 T cells with or without activation. Gene-expression data revealed that, in NKT cells, glucose is preferentially metabolized by the pentose phosphate pathway and mitochondria, as opposed to being converted into lactate. In fact, glucose is essential for the effector functions of NKT cells and a high lactate environment is detrimental for NKT cell survival and proliferation. Increased glucose uptake and IFN-γ expression in NKT cells is inversely correlated with bacterial loads in response to bacterial infection, further supporting the significance of glucose metabolism for NKT cell function. We also found that promyelocytic leukemia zinc finger seemed to play a role in regulating NKT cells’ glucose metabolism. Overall, our study reveals that NKT cells use distinct arms of glucose metabolism for their survival and function.
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Author contributions: A.K. and C.-H.C. designed research and analyzed the data; A.K., K.P., E.L.Y., and H.H. performed research; C.A.L. and S.G. contributed new reagents/analytic tools and oversaw metabolic data; and A.K., K.P., E.L.Y., C.A.L., and C.-H.C. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1901376116/-/DCSupplemental.
Published under the PNAS license.