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  The energy sensor AMPK regulates T cell metabolic adaptation and effector responses in vitro

Blagih, J., Coulombe, F., Vincent, E. E., Dupuy, F., Galicia-Vázquez, G., Yurchenko, E., et al. (2015). The energy sensor AMPK regulates T cell metabolic adaptation and effector responses in vitro. Immunity, 42, 41-54. doi:org/10.1016/j.immuni.2014.12.030.

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Blagih, Julianna1, Author
Coulombe, François1, Author
Vincent, Emma E.1, Author
Dupuy, Fanny1, Author
Galicia-Vázquez, Gabriela1, Author
Yurchenko, Ekaterina1, Author
Raissi, Thomas C.1, Author
van der Windt, Gerritje J.W.1, Author
Viollet, Benoit1, Author
Pearce, Erika L.2, Author           
Pelletier, Jerry1, Author
Piccirillo, Ciriaco A.1, Author
Krawczyk, Connie M.1, Author
Divangahi, Maziar1, Author
Jones, Russell G.1, Author
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1External Organizations, ou_persistent22              
2Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243648              

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 Abstract: 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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Language(s): eng - English
 Dates: 2015-01-20
 Publication Status: Issued
 Pages: -
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 Rev. Type: Peer
 Identifiers: DOI: org/10.1016/j.immuni.2014.12.030
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Title: Immunity
Source Genre: Journal
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Publ. Info: Cambridge, Mass. : Cell Press
Pages: - Volume / Issue: 42 Sequence Number: - Start / End Page: 41 - 54 Identifier: ISSN: 1074-7613
CoNE: https://pure.mpg.de/cone/journals/resource/954925604783