Immunity
Volume 42, Issue 1, 20 January 2015, Pages 41-54
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Article
The Energy Sensor AMPK Regulates T Cell Metabolic Adaptation and Effector Responses In Vivo

https://doi.org/10.1016/j.immuni.2014.12.030Get rights and content
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Highlights

  • T cells display metabolic flexibility in response to nutrient limitation

  • AMPK couples nutrient availability to T cell effector function

  • T cell metabolic adaptation is AMPKα1-dependent

  • AMPKα1 is required for primary T cell responses and cellular bioenergetics in vivo

Summary

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 AMPKα1 displayed reduced mitochondrial bioenergetics and cellular ATP in response to glucose limitation in vitro or pathogenic challenge in vivo. Finally, we demonstrated that AMPKα1 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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