Metabolic Instruction of Immunity

Cell - Tập 169 - Trang 570-586 - 2017
Michael D. Buck1,2, Ryan T. Sowell3, Susan M. Kaech3, Erika L. Pearce1
1Department of Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany
2Division of Biology and Biomedical Sciences Immunology Program, Washington University School of Medicine, St. Louis, MO 63110, USA
3Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA

Tài liệu tham khảo

Abbott, 2016, Germinal center hypoxia potentiates immunoglobulin class switch recombination, J. Immunol., 197, 4014, 10.4049/jimmunol.1601401 Adams, 2015, Big opportunities for small molecules in immuno-oncology, Nat. Rev. Drug Discov., 14, 603, 10.1038/nrd4596 Adams, 2016, Anabolism-associated mitochondrial stasis driving lymphocyte differentiation over self-renewal, Cell Rep., 17, 3142, 10.1016/j.celrep.2016.11.065 Allen, 2014, Ketogenic diets as an adjuvant cancer therapy: History and potential mechanism, Redox Biol., 2, 963, 10.1016/j.redox.2014.08.002 Araki, 2009, mTOR regulates memory CD8 T-cell differentiation, Nature, 460, 108, 10.1038/nature08155 Arpaia, 2013, Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation, Nature, 504, 451, 10.1038/nature12726 Balmer, 2016, Memory CD8(+) T cells require increased concentrations of acetate induced by stress for optimal function, Immunity, 44, 1312, 10.1016/j.immuni.2016.03.016 Bengsch, 2016, Bioenergetic insufficiencies due to metabolic alterations regulated by the inhibitory receptor PD-1 are an early driver of CD8(+) T cell exhaustion, Immunity, 45, 358, 10.1016/j.immuni.2016.07.008 Berod, 2014, De novo fatty acid synthesis controls the fate between regulatory T and T helper 17 cells, Nat. Med., 20, 1327, 10.1038/nm.3704 Brand, 2016, LDHA-associated lactic acid production blunts tumor immunosurveillance by T and NK cells, Cell Metab., 24, 657, 10.1016/j.cmet.2016.08.011 Buck, 2015, T cell metabolism drives immunity, J. Exp. Med., 212, 1345, 10.1084/jem.20151159 Buck, 2016, Mitochondrial dynamics controls T cell fate through metabolic programming, Cell, 166, 63, 10.1016/j.cell.2016.05.035 Bustamante, 1977, High aerobic glycolysis of rat hepatoma cells in culture: role of mitochondrial hexokinase, Proc. Natl. Acad. Sci. USA, 74, 3735, 10.1073/pnas.74.9.3735 Caro-Maldonado, 2014, Metabolic reprogramming is required for antibody production that is suppressed in anergic but exaggerated in chronically BAFF-exposed B cells, J. Immunol., 192, 3626, 10.4049/jimmunol.1302062 Cham, 2008, Glucose deprivation inhibits multiple key gene expression events and effector functions in CD8+ T cells, Eur. J. Immunol., 38, 2438, 10.1002/eji.200838289 Champagne, 2016, Fine-tuning of CD8(+) T cell mitochondrial metabolism by the respiratory chain repressor MCJ dictates protection to influenza virus, Immunity, 44, 1299, 10.1016/j.immuni.2016.02.018 Chang, 2013, Posttranscriptional control of T cell effector function by aerobic glycolysis, Cell, 153, 1239, 10.1016/j.cell.2013.05.016 Chang, 2015, Metabolic competition in the tumor microenvironment is a driver of cancer progression, Cell, 162, 1229, 10.1016/j.cell.2015.08.016 Cho, 2016, Germinal centre hypoxia and regulation of antibody qualities by a hypoxia response system, Nature, 537, 234, 10.1038/nature19334 Cinti, 2005, Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans, J. Lipid Res., 46, 2347, 10.1194/jlr.M500294-JLR200 Clever, 2016, Oxygen sensing by T cells establishes an immunologically tolerant metastatic niche, Cell, 166, 1117, 10.1016/j.cell.2016.07.032 Cogliati, 2013, Mitochondrial cristae shape determines respiratory chain supercomplexes assembly and respiratory efficiency, Cell, 155, 160, 10.1016/j.cell.2013.08.032 Colegio, 2014, Functional polarization of tumour-associated macrophages by tumour-derived lactic acid, Nature, 513, 559, 10.1038/nature13490 Condamine, 2016, Lectin-type oxidized LDL receptor-1 distinguishes population of human polymorphonuclear myeloid-derived suppressor cells in cancer patients, Sci. Immunol., 1, aaf8943, 10.1126/sciimmunol.aaf8943 Cubillos-Ruiz, 2015, ER stress sensor XBP1 controls anti-tumor immunity by disrupting dendritic cell homeostasis, Cell, 161, 1527, 10.1016/j.cell.2015.05.025 Cui, 2015, IL-7-induced glycerol transport and TAG synthesis promotes memory CD8+ T cell longevity, Cell, 161, 750, 10.1016/j.cell.2015.03.021 Dang, 2011, Control of T(H)17/T(reg) balance by hypoxia-inducible factor 1, Cell, 146, 772, 10.1016/j.cell.2011.07.033 De Rosa, 2015, Glycolysis controls the induction of human regulatory T cells by modulating the expression of FOXP3 exon 2 splicing variants, Nat. Immunol., 16, 1174, 10.1038/ni.3269 DeBerardinis, 2016, Fundamentals of cancer metabolism, Sci. Adv., 2, e1600200, 10.1126/sciadv.1600200 Delgoffe, 2009, The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment, Immunity, 30, 832, 10.1016/j.immuni.2009.04.014 Doedens, 2013, Hypoxia-inducible factors enhance the effector responses of CD8(+) T cells to persistent antigen, Nat. Immunol., 14, 1173, 10.1038/ni.2714 Doughty, 2006, Antigen receptor-mediated changes in glucose metabolism in B lymphocytes: role of phosphatidylinositol 3-kinase signaling in the glycolytic control of growth, Blood, 107, 4458, 10.1182/blood-2005-12-4788 Dufort, 2007, Cutting edge: IL-4-mediated protection of primary B lymphocytes from apoptosis via Stat6-dependent regulation of glycolytic metabolism, J. Immunol., 179, 4953, 10.4049/jimmunol.179.8.4953 Dufort, 2014, Glucose-dependent de novo lipogenesis in B lymphocytes: a requirement for atp-citrate lyase in lipopolysaccharide-induced differentiation, J. Biol. Chem., 289, 7011, 10.1074/jbc.M114.551051 Eales, 2016, Hypoxia and metabolic adaptation of cancer cells, Oncogenesis, 5, e190, 10.1038/oncsis.2015.50 Febbraio, 2014, Role of interleukins in obesity: implications for metabolic disease, Trends Endocrinol. Metab., 25, 312, 10.1016/j.tem.2014.02.004 Finlay, 2012, PDK1 regulation of mTOR and hypoxia-inducible factor 1 integrate metabolism and migration of CD8+ T cells, J. Exp. Med., 209, 2441, 10.1084/jem.20112607 Finucane, 2015, Monounsaturated fatty acid-enriched high-fat diets impede adipose NLRP3 inflammasome-mediated IL-1β secretion and insulin resistance despite obesity, Diabetes, 64, 2116, 10.2337/db14-1098 Flint, 2016, Tumor-induced IL-6 reprograms host metabolism to suppress anti-tumor immunity, Cell Metab., 24, 672, 10.1016/j.cmet.2016.10.010 Font-Burgada, 2016, Obesity and cancer: the oil that feeds the flame, Cell Metab., 23, 48, 10.1016/j.cmet.2015.12.015 Furusawa, 2013, Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells, Nature, 504, 446, 10.1038/nature12721 Geiger, 2016, L-arginine modulates T cell metabolism and enhances survival and anti-tumor activity, Cell, 167, 829, 10.1016/j.cell.2016.09.031 Gerriets, 2016, Foxp3 and Toll-like receptor signaling balance Treg cell anabolic metabolism for suppression, Nat. Immunol., 17, 1459, 10.1038/ni.3577 Goveia, 2014, Principles of targeting endothelial cell metabolism to treat angiogenesis and endothelial cell dysfunction in disease, EMBO Mol. Med., 6, 1105, 10.15252/emmm.201404156 Gubser, 2013, Rapid effector function of memory CD8+ T cells requires an immediate-early glycolytic switch, Nat. Immunol., 14, 1064, 10.1038/ni.2687 Guo, 2015, Inflammasomes: mechanism of action, role in disease, and therapeutics, Nat. Med., 21, 677, 10.1038/nm.3893 Haas, 2015, Lactate regulates metabolic and pro-inflammatory circuits in control of T cell migration and effector functions, PLoS Biol., 13, e1002202, 10.1371/journal.pbio.1002202 Haghikia, 2015, Dietary fatty acids directly impact central nervous system autoimmunity via the small intestine, Immunity, 43, 817, 10.1016/j.immuni.2015.09.007 Hand, 2016, Linking the microbiota, chronic disease, and the immune system, Trends Endocrinol. Metab., 27, 831, 10.1016/j.tem.2016.08.003 Hatfield, 2015, Immunological mechanisms of the antitumor effects of supplemental oxygenation, Sci. Transl. Med., 7, 277ra230, 10.1126/scitranslmed.aaa1260 Hensley, 2016, Metabolic heterogeneity in human lung tumors, Cell, 164, 681, 10.1016/j.cell.2015.12.034 Hernandez, 2015, Sodium chloride inhibits the suppressive function of FOXP3+ regulatory T cells, J. Clin. Invest., 125, 4212, 10.1172/JCI81151 Ho, 2015, Phosphoenolpyruvate is a metabolic checkpoint of anti-tumor T cell responses, Cell, 162, 1217, 10.1016/j.cell.2015.08.012 Hotamisligil, 2017, Inflammation, metaflammation and immunometabolic disorders, Nature, 542, 177, 10.1038/nature21363 Hsu, 2016, Lung cancer-derived galectin-1 contributes to cancer associated fibroblast-mediated cancer progression and immune suppression through TDO2/kynurenine axis, Oncotarget, 7, 27584, 10.18632/oncotarget.8488 Hu, 2016, Phosphoinositide 3-kinase regulates glycolysis through mobilization of aldolase from the actin cytoskeleton, Cell, 164, 433, 10.1016/j.cell.2015.12.042 Jang, 2015, Mitochondrial function provides instructive signals for activation-induced B-cell fates, Nat. Commun., 6, 6750, 10.1038/ncomms7750 Jellusova, 2016, The PI3K pathway in B cell metabolism, Crit. Rev. Biochem. Mol. Biol., 51, 359, 10.1080/10409238.2016.1215288 Jellusova, 2017, Gsk3 is a metabolic checkpoint regulator in B cells, Nat. Immunol., 18, 303, 10.1038/ni.3664 Jin, 2016, Glutaminolysis as a target for cancer therapy, Oncogene, 35, 3619, 10.1038/onc.2015.447 Johnston, 2009, Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation, Science, 325, 1006, 10.1126/science.1175870 Kaiko, 2016, The colonic crypt protects stem cells from microbiota-derived metabolites, Cell, 165, 1708, 10.1016/j.cell.2016.05.018 Kaplan, 2015, The development and in vivo function of T helper 9 cells, Nat. Rev. Immunol., 15, 295, 10.1038/nri3824 Kawalekar, 2016, Distinct signaling of coreceptors regulates specific metabolism pathways and impacts memory development in CAR T cells, Immunity, 44, 380, 10.1016/j.immuni.2016.01.021 Keating, 2013, The kinase mTOR modulates the antibody response to provide cross-protective immunity to lethal infection with influenza virus, Nat. Immunol., 14, 1266, 10.1038/ni.2741 Kim, 2016, Gut microbial metabolites fuel host antibody responses, Cell Host Microbe, 20, 202, 10.1016/j.chom.2016.07.001 Kleffel, 2015, Melanoma cell-intrinsic PD-1 receptor functions promote tumor growth, Cell, 162, 1242, 10.1016/j.cell.2015.08.052 Kopf, 2007, Rapamycin inhibits differentiation of Th17 cells and promotes generation of FoxP3+ T regulatory cells, Int. Immunopharmacol., 7, 1819, 10.1016/j.intimp.2007.08.027 Krawczyk, 2010, Toll-like receptor-induced changes in glycolytic metabolism regulate dendritic cell activation, Blood, 115, 4742, 10.1182/blood-2009-10-249540 Kühn, 1993, Interleukin-10-deficient mice develop chronic enterocolitis, Cell, 75, 263, 10.1016/0092-8674(93)80068-P Kunisawa, 2015, Mode of bioenergetic metabolism during B cell differentiation in the intestine determines the distinct requirement for vitamin B1, Cell Rep., 13, 122, 10.1016/j.celrep.2015.08.063 Kurashima, 2017, Mucosal ecological network of epithelium and immune cells for gut homeostasis and tissue healing, Annu. Rev. Immunol., 10.1146/annurev-immunol-051116-052424 Laidlaw, 2015, Production of IL-10 by CD4(+) regulatory T cells during the resolution of infection promotes the maturation of memory CD8(+) T cells, Nat. Immunol., 16, 871, 10.1038/ni.3224 Lam, 2016, Mitochondrial pyruvate import promotes long-term survival of antibody-secreting plasma cells, Immunity, 45, 60, 10.1016/j.immuni.2016.06.011 Lee, 2002, Tryptophan deprivation sensitizes activated T cells to apoptosis prior to cell division, Immunology, 107, 452, 10.1046/j.1365-2567.2002.01526.x Lee, 2013, Requirement for Rictor in homeostasis and function of mature B lymphoid cells, Blood, 122, 2369, 10.1182/blood-2013-01-477505 Lim, 2010, Sirtuin 1 modulates cellular responses to hypoxia by deacetylating hypoxia-inducible factor 1α, Mol. Cell, 38, 864, 10.1016/j.molcel.2010.05.023 Liu, 2014, SIRT1 limits the function and fate of myeloid-derived suppressor cells in tumors by orchestrating HIF-1α-dependent glycolysis, Cancer Res., 74, 727, 10.1158/0008-5472.CAN-13-2584 Ma, 2017, Serine is an essential metabolite for effector T cell expansion, Cell Metab., 25, 345, 10.1016/j.cmet.2016.12.011 Macintyre, 2014, The glucose transporter Glut1 is selectively essential for CD4 T cell activation and effector function, Cell Metab., 20, 61, 10.1016/j.cmet.2014.05.004 MacIver, 2013, Metabolic regulation of T lymphocytes, Annu. Rev. Immunol., 31, 259, 10.1146/annurev-immunol-032712-095956 Man, 2017, Tissue immunometabolism: development, physiology, and pathobiology, Cell Metab., 25, 11, 10.1016/j.cmet.2016.08.016 McLaughlin, 2017, Role of innate and adaptive immunity in obesity-associated metabolic disease, J. Clin. Invest., 127, 5, 10.1172/JCI88876 Michalek, 2011, Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets, J. Immunol., 186, 3299, 10.4049/jimmunol.1003613 Milasta, 2016, Apoptosis-inducing-factor-dependent mitochondrial function is required for T cell but not B cell function, Immunity, 44, 88, 10.1016/j.immuni.2015.12.002 Monticelli, 2016, Arginase 1 is an innate lymphoid-cell-intrinsic metabolic checkpoint controlling type 2 inflammation, Nat. Immunol., 17, 656, 10.1038/ni.3421 Moon, 2016, NOX4-dependent fatty acid oxidation promotes NLRP3 inflammasome activation in macrophages, Nat. Med., 22, 1002, 10.1038/nm.4153 Munn, 2002, Potential regulatory function of human dendritic cells expressing indoleamine 2,3-dioxygenase, Science, 297, 1867, 10.1126/science.1073514 Newton, 2016, Immunometabolism of regulatory T cells, Nat. Immunol., 17, 618, 10.1038/ni.3466 Nieman, 2011, Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth, Nat. Med., 17, 1498, 10.1038/nm.2492 Noman, 2014, PD-L1 is a novel direct target of HIF-1α, and its blockade under hypoxia enhanced MDSC-mediated T cell activation, J. Exp. Med., 211, 781, 10.1084/jem.20131916 Nurieva, 2009, Bcl6 mediates the development of T follicular helper cells, Science, 325, 1001, 10.1126/science.1176676 O’Neill, 2016, Immunometabolism governs dendritic cell and macrophage function, J. Exp. Med., 213, 15, 10.1084/jem.20151570 O’Neill, 2016, A guide to immunometabolism for immunologists, Nat. Rev. Immunol., 16, 553, 10.1038/nri.2016.70 O’Sullivan, 2014, Memory CD8(+) T cells use cell-intrinsic lipolysis to support the metabolic programming necessary for development, Immunity, 41, 75, 10.1016/j.immuni.2014.06.005 Odegaard, 2007, Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance, Nature, 447, 1116, 10.1038/nature05894 Oestreich, 2014, Bcl-6 directly represses the gene program of the glycolysis pathway, Nat. Immunol., 15, 957, 10.1038/ni.2985 Pan, 2017, Survival of tissue-resident memory T cells requires exogenous lipid uptake and metabolism, Nature, 543, 252, 10.1038/nature21379 Park, 2010, Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression, Cell, 140, 197, 10.1016/j.cell.2009.12.052 Parry, 2005, CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms, Mol. Cell. Biol., 25, 9543, 10.1128/MCB.25.21.9543-9553.2005 Patsoukis, 2015, PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation, Nat. Commun., 6, 6692, 10.1038/ncomms7692 Pearce, 2009, Enhancing CD8 T-cell memory by modulating fatty acid metabolism, Nature, 460, 103, 10.1038/nature08097 Pearce, 2013, Fueling immunity: insights into metabolism and lymphocyte function, Science, 342, 1242454, 10.1126/science.1242454 Peng, 2016, Aerobic glycolysis promotes T helper 1 cell differentiation through an epigenetic mechanism, Science, 354, 481, 10.1126/science.aaf6284 Pérez-Escuredo, 2016, Lactate promotes glutamine uptake and metabolism in oxidative cancer cells, Cell Cycle, 15, 72, 10.1080/15384101.2015.1120930 Phan, 2016, Constitutive glycolytic metabolism supports CD8(+) T cell effector memory differentiation during viral infection, Immunity, 45, 1024, 10.1016/j.immuni.2016.10.017 Pollizzi, 2016, Asymmetric inheritance of mTORC1 kinase activity during division dictates CD8(+) T cell differentiation, Nat. Immunol., 17, 704, 10.1038/ni.3438 Porporato, 2016, Understanding cachexia as a cancer metabolism syndrome, Oncogenesis, 5, e200, 10.1038/oncsis.2016.3 Ramakrishnan, 2014, Oxidized lipids block antigen cross-presentation by dendritic cells in cancer, J. Immunol., 192, 2920, 10.4049/jimmunol.1302801 Rao, 2017, Pathogen-mediated inhibition of anorexia promotes host survival and transmission, Cell, 168, 503, 10.1016/j.cell.2017.01.006 Rathinam, 2016, Inflammasome complexes: emerging mechanisms and effector functions, Cell, 165, 792, 10.1016/j.cell.2016.03.046 Ray, 2015, The interleukin-2-mTORc1 kinase axis defines the signaling, differentiation, and metabolism of T helper 1 and follicular B helper T cells, Immunity, 43, 690, 10.1016/j.immuni.2015.08.017 Reboldi, 2016, Peyer’s patches: organizing B-cell responses at the intestinal frontier, Immunol. Rev., 271, 230, 10.1111/imr.12400 Ribas, 2015, Releasing the brakes on cancer immunotherapy, N. Engl. J. Med., 373, 1490, 10.1056/NEJMp1510079 Rodriguez, 2004, Arginase I production in the tumor microenvironment by mature myeloid cells inhibits T-cell receptor expression and antigen-specific T-cell responses, Cancer Res., 64, 5839, 10.1158/0008-5472.CAN-04-0465 Ron-Harel, 2016, Mitochondrial biogenesis and proteome remodeling promote one-carbon metabolism for T cell activation, Cell Metab., 24, 104, 10.1016/j.cmet.2016.06.007 Rooks, 2016, Gut microbiota, metabolites and host immunity, Nat. Rev. Immunol., 16, 341, 10.1038/nri.2016.42 Saltiel, 2017, Inflammatory mechanisms linking obesity and metabolic disease, J. Clin. Invest., 127, 1, 10.1172/JCI92035 Scharping, 2016, The tumor microenvironment represses T cell mitochondrial biogenesis to drive intratumoral T cell metabolic insufficiency and dysfunction, Immunity, 45, 374, 10.1016/j.immuni.2016.07.009 Scharping, 2017, Efficacy of PD-1 blockade is potentiated by metformin-induced reduction of tumor hypoxia, Cancer Immunol. Res., 5, 9, 10.1158/2326-6066.CIR-16-0103 Schultz, 2010, Effects of inhibition of interleukin-6 signalling on insulin sensitivity and lipoprotein (a) levels in human subjects with rheumatoid diseases, PLoS ONE, 5, e14328, 10.1371/journal.pone.0014328 Sena, 2013, Mitochondria are required for antigen-specific T cell activation through reactive oxygen species signaling, Immunity, 38, 225, 10.1016/j.immuni.2012.10.020 Shi, 2011, HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells, J. Exp. Med., 208, 1367, 10.1084/jem.20110278 Shouval, 2014, Interleukin-10 receptor signaling in innate immune cells regulates mucosal immune tolerance and anti-inflammatory macrophage function, Immunity, 40, 706, 10.1016/j.immuni.2014.03.011 Sinclair, 2013, Control of amino-acid transport by antigen receptors coordinates the metabolic reprogramming essential for T cell differentiation, Nat. Immunol., 14, 500, 10.1038/ni.2556 Smith, 2013, The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis, Science, 341, 569, 10.1126/science.1241165 Sonveaux, 2008, Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice, J. Clin. Invest., 118, 3930 Spencer, 1998, The orphan receptor CRF2-4 is an essential subunit of the interleukin 10 receptor, J. Exp. Med., 187, 571, 10.1084/jem.187.4.571 Staron, 2014, The transcription factor FoxO1 sustains expression of the inhibitory receptor PD-1 and survival of antiviral CD8(+) T cells during chronic infection, Immunity, 41, 802, 10.1016/j.immuni.2014.10.013 Sukumar, 2013, Inhibiting glycolytic metabolism enhances CD8+ T cell memory and antitumor function, J. Clin. Invest., 123, 4479, 10.1172/JCI69589 Swamy, 2016, Glucose and glutamine fuel protein O-GlcNAcylation to control T cell self-renewal and malignancy, Nat. Immunol., 17, 712, 10.1038/ni.3439 Takeda, 1999, Enhanced Th1 activity and development of chronic enterocolitis in mice devoid of Stat3 in macrophages and neutrophils, Immunity, 10, 39, 10.1016/S1074-7613(00)80005-9 Torres, 2016, Asparagine deprivation mediated by Salmonella asparaginase causes suppression of activation-induced T cell metabolic reprogramming, J. Leukoc. Biol., 99, 387, 10.1189/jlb.4A0615-252R Tyrakis, 2016, S-2-hydroxyglutarate regulates CD8(+) T-lymphocyte fate, Nature, 540, 236, 10.1038/nature20165 Uyttenhove, 2003, Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase, Nat. Med., 9, 1269, 10.1038/nm934 van der Windt, 2012, Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development, Immunity, 36, 68, 10.1016/j.immuni.2011.12.007 Verbist, 2016, Metabolic maintenance of cell asymmetry following division in activated T lymphocytes, Nature, 532, 389, 10.1038/nature17442 Vesely, 2013, Cancer immunoediting: antigens, mechanisms, and implications to cancer immunotherapy, Ann. N Y Acad. Sci., 1284, 1, 10.1111/nyas.12105 Vuillefroy de Silly, 2016, Hypoxia and antitumor CD8(+) T cells: An incompatible alliance?, OncoImmunology, 5, e1232236, 10.1080/2162402X.2016.1232236 Wang, 2011, The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation, Immunity, 35, 871, 10.1016/j.immuni.2011.09.021 Wang, 2015, CD5L/AIM regulates lipid biosynthesis and restrains Th17 cell pathogenicity, Cell, 163, 1413, 10.1016/j.cell.2015.10.068 Wang, 2016, Opposing effects of fasting metabolism on tissue tolerance in bacterial and viral inflammation, Cell, 166, 1512, 10.1016/j.cell.2016.07.026 Wang, 2016, Histone deacetylase SIRT1 negatively regulates the differentiation of interleukin-9-producing CD4(+) T cells, Immunity, 44, 1337, 10.1016/j.immuni.2016.05.009 Wegrzyn, 2009, Function of mitochondrial Stat3 in cellular respiration, Science, 323, 793, 10.1126/science.1164551 Wenes, 2016, Macrophage metabolism controls tumor blood vessel morphogenesis and metastasis, Cell Metab., 24, 701, 10.1016/j.cmet.2016.09.008 Wherry, 2015, Molecular and cellular insights into T cell exhaustion, Nat. Rev. Immunol., 15, 486, 10.1038/nri3862 Wilhelm, 2016, Critical role of fatty acid metabolism in ILC2-mediated barrier protection during malnutrition and helminth infection, J. Exp. Med., 213, 1409, 10.1084/jem.20151448 Woodland, 2008, Multiple signaling pathways promote B lymphocyte stimulator dependent B-cell growth and survival, Blood, 111, 750, 10.1182/blood-2007-03-077222 Yang, 2016, Potentiating the antitumour response of CD8(+) T cells by modulating cholesterol metabolism, Nature, 531, 651, 10.1038/nature17412 Youm, 2015, The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease, Nat. Med., 21, 263, 10.1038/nm.3804 Zeng, 2016, mTORC1 and mTORC2 kinase signaling and glucose metabolism drive follicular helper T cell differentiation, Immunity, 45, 540, 10.1016/j.immuni.2016.08.017 Zhao, 2016, Cancer mediates effector T cell dysfunction by targeting microRNAs and EZH2 via glycolysis restriction, Nat. Immunol., 17, 95, 10.1038/ni.3313 Zhou, 2010, Differentiation and persistence of memory CD8(+) T cells depend on T cell factor 1, Immunity, 33, 229, 10.1016/j.immuni.2010.08.002 Zigmond, 2014, Macrophage-restricted interleukin-10 receptor deficiency, but not IL-10 deficiency, causes severe spontaneous colitis, Immunity, 40, 720, 10.1016/j.immuni.2014.03.012