期刊
BIOCHEMICAL SOCIETY TRANSACTIONS
卷 41, 期 -, 页码 681-686出版社
PORTLAND PRESS LTD
DOI: 10.1042/BST20120359
关键词
cytotoxic T-lymphocyte; glycolysis; hypoxia-inducible factor 1 alpha (HIF1 alpha); mammalian target of rapamycin complex 1 (mTORC1); protein kinase B (PKB); trafficking
资金
- Marie Curie Career Integration Grant [321603]
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 HIF1 alpha (hypoxia-inducible factor 1 alpha). Strikingly, HIF1 alpha 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/HIF1 alpha signalling integrates the control of T-cell metabolism and T-cell function.
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