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      Sugar, fat, and protein: new insights into what T cells crave

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      , Ph.D 1 , , M.D., Ph.D 2
      Current opinion in immunology

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          Abstract

          T cell activation and differentiation is a complex process that has evolved beyond the two-signal model to a number of varied and opposing inputs that must be interpreted to make a cell fate decision. While stimulation through the TCR, costimulatory, and cytokine receptors is required, metabolic signaling has emerged not only an activation signal, but one that can influence and shape differentiation. Recent findings have revealed unappreciated roles for glucose, fatty acids, and salt in the function of many T cell subsets. In this review, we will highlight the latest advances in the burgeoning field of immunometabolism, focusing on how the menu of T cell fuels has expanded.

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          Most cited references35

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          On the origin of cancer cells.

          O WARBURG (1956)
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            Fueling immunity: insights into metabolism and lymphocyte function.

            Lymphocytes face major metabolic challenges upon activation. They must meet the bioenergetic and biosynthetic demands of increased cell proliferation and also adapt to changing environmental conditions, in which nutrients and oxygen may be limiting. An emerging theme in immunology is that metabolic reprogramming and lymphocyte activation are intricately linked. However, why T cells adopt specific metabolic programs and the impact that these programs have on T cell function and, ultimately, immunological outcome remain unclear. Research on tumor cell metabolism has provided valuable insight into metabolic pathways important for cell proliferation and the influence of metabolites themselves on signal transduction and epigenetic programming. In this Review, we highlight emerging concepts regarding metabolic reprogramming in proliferating cells and discuss their potential impact on T cell fate and function.
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              The glucose transporter Glut1 is selectively essential for CD4 T cell activation and effector function.

              CD4 T cell activation leads to proliferation and differentiation into effector (Teff) or regulatory (Treg) cells that mediate or control immunity. While each subset prefers distinct glycolytic or oxidative metabolic programs in vitro, requirements and mechanisms that control T cell glucose uptake and metabolism in vivo are uncertain. Despite expression of multiple glucose transporters, Glut1 deficiency selectively impaired metabolism and function of thymocytes and Teff. Resting T cells were normal until activated, when Glut1 deficiency prevented increased glucose uptake and glycolysis, growth, proliferation, and decreased Teff survival and differentiation. Importantly, Glut1 deficiency decreased Teff expansion and the ability to induce inflammatory disease in vivo. Treg cells, in contrast, were enriched in vivo and appeared functionally unaffected and able to suppress Teff, irrespective of Glut1 expression. These data show a selective in vivo requirement for Glut1 in metabolic reprogramming of CD4 T cell activation and Teff expansion and survival. Copyright © 2014 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Journal
                8900118
                1461
                Curr Opin Immunol
                Curr. Opin. Immunol.
                Current opinion in immunology
                0952-7915
                1879-0372
                3 March 2015
                6 February 2015
                April 2015
                01 April 2016
                : 33
                : 49-54
                Affiliations
                [1 ]Tumor Microenvironment Center, Department of Immunology, University of Pittsburgh Cancer Institute, Pittsburgh, PA
                [2 ]Sidney-Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD
                Article
                NIHMS662362
                10.1016/j.coi.2015.01.015
                4397153
                25665466
                fdc77d12-49a2-4be1-9765-b1476bab379c
                © 2015 Published by Elsevier Ltd.

                This manuscript version is made available under the CC BY-NC-ND 4.0 license.

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                Immunology
                Immunology

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