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The Energy Sensor AMPK Regulates T Cell Metabolic Adaptation and Effector Responses In Vivo

2015; Cell Press; Volume: 42; Issue: 1 Linguagem: Inglês

10.1016/j.immuni.2014.12.030

1097-4180

Julianna Blagih, François Coulombe, Emma E. Vincent, Fanny Dupuy, Gabriela Galicia-Vázquez, Ekaterina A. Yurchenko, Thomas C. Raissi, Gerritje J. W. van der Windt, Benoı̂t Viollet, Erika L. Pearce, Jerry Pelletier, Ciriaco A. Piccirillo, Connie M. Krawczyk, Maziar Divangahi, Russell G. Jones,

Immune Cell Function and Interaction

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.