Given that inflammatory T-cells have a highly glycolytic metabolism, whereas regulatory T-cells rely more on oxidative glucose metabolism, there is growing interest in understanding how T-cell metabolism relates to T-cell function. The mTORC1 (mammalian target of rapamycin complex 1) has a crucial role to determine the balance between effector and regulatory T-cell differentiation, but is also described as a key regulator of metabolism in non-immune cell systems. The present review explores the relationship between these diverse functions of mTORC1 with regard to T-cell function. In many cell systems, mTORC1 couples PI3K (phosphoinositide 3-kinase) and PKB (protein kinase B), also known as Akt, with the control of glucose uptake and glycolysis. However, this is not the case in activated CD8+ CTLs (cytotoxic T-lymphocytes) where PI3K/PKB signalling is dispensable for the elevated levels of glycolysis that is characteristic of activated T-cells. Nevertheless, mTORC1 is still essential for glycolytic metabolism in CD8+ T-cells, and this reflects the fact that mTORC1 does not lie downstream of PI3K/PKB signalling in CD8+ T-cells, as is the case in many other cell systems. mTORC1 regulates glucose metabolism in CTLs through regulating the expression of the transcription factor HIF1α (hypoxia-inducible factor 1α). Strikingly, HIF1α functions to couple mTORC1 with a diverse transcriptional programme that extends beyond the control of glucose metabolism to the regulation of multiple key T-cell functions. The present review discusses the idea that mTORC1/HIF1α signalling integrates the control of T-cell metabolism and T-cell function.
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Conference Article|
March 21 2013
mTORC1 regulates CD8+ T-cell glucose metabolism and function independently of PI3K and PKB
David K. Finlay
David K. Finlay
1
1School of Biochemistry and Immunology, and School of Pharmacy and Pharmaceutical Sciences, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland
1emailfinlayd@tcd.ie
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Publisher: Portland Press Ltd
Received:
December 19 2012
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2013 Biochemical Society
2013
Biochem Soc Trans (2013) 41 (2): 681–686.
Article history
Received:
December 19 2012
Citation
David K. Finlay; mTORC1 regulates CD8+ T-cell glucose metabolism and function independently of PI3K and PKB. Biochem Soc Trans 1 April 2013; 41 (2): 681–686. doi: https://doi.org/10.1042/BST20120359
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