期刊
IMMUNITY
卷 42, 期 1, 页码 41-54出版社
CELL PRESS
DOI: 10.1016/j.immuni.2014.12.030
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资金
- Canadian Institutes of Health Research (CIHR)
- Fonds de Recherche du Quebec-Sante (FRQS)
- McGill Integrated Cancer Research Training Program (MICRTP)
- NIAID [5R01AI091965]
- Arthritis Society [RG-11-017]
- CIHR [MOP-93799]
Naive T cells undergo metabolic reprogramming to support the increased energetic and biosynthetic demands of effector T cell function. However, how nutrient availability influences T cell metabolism and function remains poorly understood. Here we report plasticity in effector T cell metabolism in response to changing nutrient availability. Activated T cells were found to possess a glucose-sensitive metabolic checkpoint controlled by the energy sensor AMP-activated protein kinase (AMPK) that regulated mRNA translation and glutamine-dependent mitochondrial metabolism to maintain T cell bioenergetics and viability. T cells lacking AMPK alpha 1 displayed reduced mitochondrial bioenergetics and cellular ATP in response to glucose limitation in vitro or pathogenic challenge in vivo. Finally, we demonstrated that AMPKa1 is essential for T helper 1 (Th1) and Th17 cell development and primary T cell responses to viral and bacterial infections in vivo. Our data highlight AMPK-dependent regulation of metabolic homeostasis as a key regulator of T cell-mediated adaptive immunity.
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