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Inflammation Research

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31.07.2018 | Review

Immunometabolism of T cells and NK cells: metabolic control of effector and regulatory function

verfasst von: Sophie M. Poznanski, Nicole G. Barra, Ali A. Ashkar, Jonathan D. Schertzer

Erschienen in: Inflammation Research | Ausgabe 10/2018

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Abstract

Metabolic flux can dictate cell fate, including immune cell effector and regulatory function. The metabolic regulation of cell function is well characterized with respect to effector, memory, and regulatory T cells. This knowledge may allow for manipulation of T cell metabolic pathways that set the stage for more effective T cell therapy. Natural Killer (NK) and T-lymphocytes have complementary roles in the defense against pathogens. However, studies of NK cell metabolism are only beginning to emerge and there is comparatively little knowledge on the metabolic regulation of NK-cell activation and effector function. Given their common lymphoid lineage, effector functions and cellular memory potential our current knowledge on T cell metabolism could inform investigation of metabolic reprogramming in NK cells. In this review, we compare the current knowledge of metabolic regulation in T cell and NK cell development, activation, effector and memory function. Commonalties in glucose transport, hypoxia-inducible factors and mTOR highlight metabolic control points in both cells types. Contrasting the glycolytic and oxidative nodes of metabolic regulation in T cells versus NK cells may provide insight into the contribution of specific immune responses to disease and promote the development of immunotherapeutic approaches targeting both innate and adaptive immune responses.

Bodduluru LN, Kasala ER, Madhana RM, Sriram CS. Natural killer cells: the journey from puzzles in biology to treatment of cancer. Cancer Lett. 2015;357(2):454–67. https://doi.org/10.1016/j.canlet.2014.12.020.CrossRefPubMed

Vivier E, Tomasello E, Baratin T, Walzer T, Ugolini S. Functions of natural killer cells. Nat Immunol. 2008;9:503–10.CrossRefPubMed

Cooper MA, Elliott JM, Keyel PA, Yang L, Carrero JA, Yokoyama WM. Cytokine-induced memory-like natural killer cells. Proc Natl Acad Sci USA. 2009;106(6):1915–9.CrossRefPubMed

Chen L, Flies DB. Molecular mechanisms of T cell co-stimulation and co-inhibition. Nat Rev Immunol. 2013;13(4):227–42. https://doi.org/10.1038/nri3405.CrossRefPubMedPubMedCentral

Pearce EL, Mullen AC, Matins GA, Krawczyk CM, Hutchins AS, Zediak VP, et al. Control of effector CD8⁺ T cell function by the transcription factor eomesodermin. Science. 2003;302(5647):1041–3.CrossRefPubMed

Jiao L, Gao X, Joyee AG, Zhao L, Qiu H, Yang M, et al. NK cells promote type 1 T cell immunity through modulating the function of dendritic cells during intracellular bacterial infection. J Immunol. 2011;187(1):401–11. https://doi.org/10.4049/jimmunol.1002519.CrossRefPubMed

Cook KD, Waggoner SN, Whitmire JK. NK cells and their ability to modulate T cells during virus infections. Crit Rev Immunol. 2014;34(5):359–88.CrossRefPubMedPubMedCentral

Ye L, Jiang B, Deng J, Du J, Xiong W, Guan Y, et al. IL-37 alleviates rheumatoid arthritis by suppressing IL-17 and IL-17-triggering cytokine production and limiting Th17 cell proliferation. J Immunol. 2015;194(11):5110–9. https://doi.org/10.4049/jimmunol.1401810.CrossRefPubMed

Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD, et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med. 2005;201(2):233–40.CrossRefPubMedPubMedCentral

10.

Venkatesha SH, Dudics S, Weingartner E, So EC, Pedra J, Moudgil KD. Altered Th17/Treg balance and dysregulated IL-1β response influence susceptibility/resistance to experimental autoimmune arthritis. Int J Immunopathol Pharmacol. 2015;28(3):318–28. https://doi.org/10.1177/0394632015595757.CrossRefPubMed

11.

Berod L, Friedrich C, Nandan A, Freitag J, Hagemann S, Harmrolfs K, et al. De novo fatty acid synthesis controls the fate between regulatory T and T helper 17 cells. Nat Med. 2014;20(11):1327–33.CrossRefPubMed

12.

Gerriets VA, Kishton RJ, Johnson MO, Cohen S, Siska PJ, Nichols AG, et al. Foxp3 and Toll-like receptor signaling balance Treg cell anabolic metabolism for suppression. Nat Immunol. 2016;17(12):1459–66.CrossRefPubMedPubMedCentral

13.

Macintyre AN, Gerriets VA, Nichols AG, Michalek RD, Rudolph MC, Deoliveira D, et al. The glucose transporter Glut1 is selectively essential for CD4 T cell activation and effector function. Cell Metab. 2014;20(1):61–72.CrossRefPubMedPubMedCentral

14.

Dungan LS, McGuinness NC, Boon L, Lynch MA, Mills KH. Innate IFN-γ promotes development of experimental autoimmune encephalomyelitis: a role for NK cells and M1 macrophages. Eur J Immunol. 2014;44(10):2903–17.CrossRefPubMed

15.

Lu L, Ikizawa K, Hu D, Werneck MB, Wucherpfennig KW, Cantor H. Regulation of activated CD4⁺ T cells by NK cells via the Qa-1-NKG2A inhibitory pathway. Immunity. 2007;26(5):593–604.CrossRefPubMedPubMedCentral

16.

O’Neill LA, Kishton RJ, Rathmell J. A guide to immunometabolism for immunologists. Nat Rev Immunol. 2016;16(9):553–65. https://doi.org/10.1038/nri.2016.70.CrossRefPubMedPubMedCentral

17.

Hui S, Ghergurovich JM, Morscher RJ, Jang C, Teng X, Lu W, et al. Glucose feeds the TCA cycle via circulating lactate. Nature. 2017;551(7678):115–8. https://doi.org/10.1038/nature24057.CrossRefPubMedPubMedCentral

18.

Ciofani M, Zuniga-Pflucker JC. Notch promotes survival of pre—T cells at the beta-selection checkpoint by regulating cellular metabolism. Nat Immunol. 2005;6(9):881–8.CrossRefPubMed

19.

Swainson L, Kinet S, Manel N, Battini JL, Sitbon M, Taylor N. Glucose transporter 1 expression identifies a population of cycling CD4⁺ CD8⁺ human thymocytes with high CXCR4-induced chemotaxis. Proc Natl Acad Sci USA. 2005;102(36):12867–72.CrossRefPubMed

20.

Vigano MA, Ivanek R, Balwierz P, Berninger P, van Nimwegen E, Karjalainen K, et al. An epigenetic profile of early T-cell development from multipotent progenitors to committed T-cell descendants. Eur J Immunol. 2014;44(4):1181–93.CrossRefPubMed

21.

Peng M, Yin N, Chhangawala S, Xu K, Leslie CS, Li MO. Aerobic glycolysis promotes T helper 1 cell differentiation through an epigenetic mechanism. Science. 2016;354(6311):481–4.CrossRefPubMedPubMedCentral

22.

Chang CH, Curtis JD, Maggi LBJ, Faubert B, Villarino AV, O’Sullivan D, et al. Posttranscriptional control of T cell effector function by aerobic glycolysis. Cell. 2013;153(6):1239–51. https://doi.org/10.1016/j.cell.2013.05.016.CrossRefPubMedPubMedCentral

23.

Wang R, Dillon CP, Shi LZ, Milasta S, Carter R, Finkelstein D, et al. The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation. Immunity. 2011;35(6):871–2.CrossRefPubMedPubMedCentral

24.

Frauwirth KA, Riley JL, Harris MH, Parry RV, Rathmell JC, Plas DR, et al. The CD28 signaling pathway regulates glucose metabolism. Immunity. 2002;16(6):769–77.CrossRefPubMed

25.

Chiossone L, Chaix J, Fuseri N, Roth C, Vivier E, Walzer T. Maturation of mouse NK cells is a 4-stage developmental program. Blood. 2009;113(22):5488–96. https://doi.org/10.1182/blood-2008-10-187179.CrossRefPubMed

26.

Marcais A, Cherfils-Vicini J, Viant C, Degouve S, Viel S, Fenis A, et al. The metabolic checkpoint kinase mTOR is essential for interleukin-15 signaling during NK cell development and activation. Nat Immunol. 2014;15(8):749–57.CrossRefPubMedPubMedCentral

27.

Shaw RJ. LKB1 and AMP-activated protein kinase control of mTOR signalling and growth. Acta Physiol (Oxf). 2009;196(1):65–80. https://doi.org/10.1111/j.1748-1716.2009.01972.x.CrossRef

28.

Blagih J, Coulombe F, Vincent EE, Dupuy F, Galicia-Vazquez G, Yurchenko E, et al. The energy sensor AMPK regulates T cell metabolic adaptation and effector responses in vivo. Immunity. 2015;42(1):41–54.CrossRefPubMed

29.

Michalek RD, Gerriets VA, Jacobs SR, Macintyre AN, Mason NJ, Mason EF, et al. Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4⁺ T cell subsets. J Immunol. 2011;186(6):3299–303.CrossRefPubMedPubMedCentral

30.

Lee JS, Walsh MC, Hoehn KL, James DE, Wherry EJ, Choi Y. Regulator of fatty acid metabolism, acetyl coenzyme a carboxylase 1, controls T cell immunity. J Immunol. 2014;192(7):3190–9.CrossRefPubMedPubMedCentral

31.

Shi LZ, Wang R, Huang G, Vogel P, Neale G, Green DR, et al. HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. J Exp Med. 2011;208(7):1367–76.CrossRefPubMedPubMedCentral

32.

Mahnke J, Schumacher V, Ahrens S, Käding N, Feldhoff LM, Huber M, et al. Interferon regulatory factor 4 controls TH1 cell effector function and metabolism. Sci Rep. 2016;6:35521.CrossRefPubMedPubMedCentral

33.

Kong X, Banks A, Liu T, Kazak L, Rao RR, Cohen P, et al. IRF4 is a key thermogenic transcriptional partner of PGC-1α. Cell. 2014;158(1):69–83. https://doi.org/10.1016/j.cell.2014.04.049.CrossRefPubMedPubMedCentral

34.

Eguchi J, Wang X, Yu S, Kershaw EE, Chiu PC, Dushay J, et al. Transcriptional control of adipose lipid handling by IRF4. Cell Metab. 2011;13(3):249–59.CrossRefPubMedPubMedCentral

35.

Cavallari JF, Fullerton MD, Duggan BM, Foley KP, Denou E, Smith BK, et al. Muramyl dipeptide-based postbiotics mitigate obesity-induced insulin resistance via IRF4. Cell Metab. 2017;25(5):1063–74. https://doi.org/10.1016/j.cmet.2017.03.021.CrossRefPubMed

36.

Carr EL, Kelman A, Wu GS, Gopaul R, Senkevitch E, Aghvanyan A, et al. Glutamine uptake and metabolism are coordinately regulated by ERK/MAPK during T lymphocyte activation. J Immunol. 2010;185(2):1037–44. https://doi.org/10.4049/jimmunol.0903586.CrossRefPubMedPubMedCentral

37.

Hayashi K, Jutabha P, Endou H, Sagara H, Anzai N. LAT1 is a critical transporter of essential amino acids for immune reactions in activated human T cells. J Immunol. 2013;191(8):4080–5. https://doi.org/10.4049/jimmunol.1300923.CrossRefPubMed

38.

Sinclair LV, Rolf J, Emslie E, Shi YB, Taylor PM, Cantrell DA. Control of amino-acid transport by antigen receptors coordinates the metabolic reprogramming essential for T cell differentiation. Nat Immunol. 2013;14(5):500–8. https://doi.org/10.1038/ni.2556.CrossRefPubMedPubMedCentral

39.

Ma EH, Bantug G, Griss T, Condotta S, Johnson RM, Samborska B, et al. Serine is an essential metabolite for effector T cell expansion. Cell Metab. 2017;25(2):345–57. https://doi.org/10.1016/j.cmet.2016.12.011.CrossRefPubMed

40.

Klysz D, Tai X, Robert PA, Craveiro M, Cretenet G, Oburoglu L, et al. Glutamine-dependent alpha-ketoglutarate production regulates the balance between T helper 1 cell and regulatory T cell generation. Sci Signal. 2015;8(396):ra97. https://doi.org/10.1126/scisignal.aab2610.CrossRefPubMed

41.

Nakaya M, Xiao Y, Zhou X, Chang JH, Chang M, Cheng X, et al. Inflammatory T cell responses rely on amino acid transporter ASCT2 facilitation of glutamine uptake and mTORC1 kinase activation. Immunity. 2014;40(5):692–705. https://doi.org/10.1016/j.immuni.2014.04.007.CrossRefPubMedPubMedCentral

42.

Ho PC, Bihuniak JD, Macintyre AN, Staron M, Liu X, Amezquita R, et al. Phosphoenolpyruvate is a metabolic checkpoint of anti-tumour T cell responses. Cell. 2015;162(6):1217–28.CrossRefPubMedPubMedCentral

43.

Salerno F, Guislain A, Cansever D, Wolers MC. TLR-mediated innate production of IFN-γ by CD8⁺ T cells is independent of glycolysis. J Immunol. 2016;196(9):3695–705.CrossRefPubMed

44.

Donnelly RP, Loftus RM, Keating SE, Liou KT, Biron CA, Gardiner CM, et al. mTORC1-dependent metabolic reprogramming is a prerequisite for NK cell effector function. J Immunol. 2014;193:4477–84.CrossRefPubMedPubMedCentral

45.

Keating SE, Zaiatz-Bittencourt V, Loftus RM, Keane C, Brennan K, Finlay DK, et al. Metabolic reprogramming supports IFN-γ production by CD56bright NK cells. J Immunol. 2016;196(6):2552–60. https://doi.org/10.4049/jimmunol.1501783.CrossRefPubMed

46.

Keppel MP, Saucier N, Mah AY, Vogel TP, Cooper MA. Activation-specific metabolic requirements for NK cell IFN-g production. J Immunol. 2015;194(4):1954–62.CrossRefPubMedPubMedCentral

47.

Assmann N, O’Brien KL, Donnelly RP, Dyck L, Zaiatz-Bittencourt V, Loftus RM, et al. Srebp-controlled glucose metabolism is essential for NK cell functional responses. Nat Immunol. 2017;18(11):1197–206. https://doi.org/10.1038/ni.3838.CrossRefPubMed

48.

Mao Y, van Hoef V, Zhang X, Wennerberg E, Lorent J, Witt K, et al. IL-15 activates mTOR and primes stress-activated gene-expression leading to prolonged anti-tumor capacity of NK cells. Blood. 2016;128(11):1475–89. https://doi.org/10.1182/blood-2016-02-698027.CrossRefPubMedPubMedCentral

49.

Cham CM, Gajewski TF. Glucose availability regulates IFN-gamma production and p70S6 kinase activation in CD8⁺ effector T cells. J Immunol. 2005;174(8):4670–7.CrossRefPubMed

50.

Walker W, Aste-Amezaga M, Kastelein RA, Trinchieri G, Hunter CA. IL-18 and CD28 use distinct molecular mechanisms to enhance NK cell production of IL-12-induced IFN-gamma. J Immunol. 1999;162(10):5894–901.PubMed

51.

Nielsen CM, Wolf AS, Goodier MR, Riley EM. Synergy between common γ chain family cytokines and IL-18 potentiates innate and adaptive pathways of NK cell activation. Front Immunol. 2016;7(101). https://doi.org/10.3389/fimmu.2016.00101.

52.

Tsurutani N, Mittal P, St Rose MC, Ngoi SM, Svedova J, Menoret A, et al. Costimulation endows immunotherapeutic CD8 T cells with IL-36 responsiveness during aerobic glycolysis. J Immunol. 2016;196(1):124–34.CrossRefPubMed

53.

O’Sullivan D, van der Windt GJ, Huang SC, Curtis JD, Chang CH, Buck MD, et al. Memory CD8(+) T cells use cell-intrinsic lipolysis to support the metabolic programming necessary for development. Immunity. 2014;41(1):75–88.CrossRefPubMedPubMedCentral

54.

Buck MD, O’Sullivan D, Klein Geltink RI, Curtis JD, Chang CH, Sanin DE, et al. Mitochondrial dynamics controls T cell fate through metabolic programming. Cell. 2016;166(1):63–76.CrossRefPubMedPubMedCentral

55.

Pearce EL, Walsh MC, Cejas PJ, Harms GM, Shen H, Wang LS, et al. Enhancing CD8 T-cell memory by modulating fatty acid metabolism. Nature. 2009;460(7251):103–7.CrossRefPubMedPubMedCentral

56.

van der Windt GJ, Everts B, Chang CH, Curtis JD, Freitas TC, Amiel E, et al. Mitochondrial respiratory capacity is a critical regulator of CD8⁺ T cell memory development. Immunity. 2012;31(1):68–78.

57.

Gubser PM, Bantug GR, Razik L, Fischer M, Dimeloe S, Hoenger G, et al. Rapid effector function of memory CD8⁺ T cells requires an immediate-early glycolytic switch. Nat Immunol. 2013;14(10):1064–72.CrossRefPubMed

58.

Beier UH, Angelin A, Akimova T, Wang LS, Liu Y, Xiao H, et al. Essential role of mitochondrial energy metabolism in Foxp3⁺ T-regulatory cell function and allograft survival. FASEB J. 2015;29(6):2315–26.CrossRefPubMedPubMedCentral

59.

Shrestha S, Yang K, Guy C, Vogel P, Neale G, Chi H. Treg cells require the phosphatase PTEN to restrain TH1 and TFH cell responses. Nat Immunol. 2015;16(2):178–87.CrossRefPubMedPubMedCentral

60.

Prlic M, Williams MA, Bevan MJ. Requirements for CD8 T-cell priming, memory generation and maintenance. Curr Opin Immunol. 2007;19(3):315–9.CrossRefPubMed

61.

King CG, Kobayashi T, Cejas PJ, Kim T, Yoon K, Kim GK, et al. TRAF6 is a T cell-intrinsic negative regulator required for the maintenance of immune homeostasis. Nat Med. 2006;12(9):1088–92.CrossRefPubMed

62.

Araki K, Turner AP, Shaffer VO, Gangappa S, Keller SA, Bachmann MF, et al. mTOR regulates memory CD8 T-cell differentiation. Nature. 2009;460(7251):108–12. https://doi.org/10.1038/nature08155.CrossRefPubMedPubMedCentral

63.

Sun JC, Beilke JN, Lanier LL. Adaptive immune features of natural killer cells. Nature. 2009;457(7229):557–61. https://doi.org/10.1038/nature07665.CrossRefPubMedPubMedCentral

64.

Romee R, Rosario M, Berrien-Elliott MM, Wagner JA, Jewell BA, Schappe T, et al. Cytokine-induced memory-like natural killer cells exhibit enhanced responses against myeloid leukemia. Sci Transl Med. 2016;8(357):357ra123.CrossRefPubMedPubMedCentral

65.

O’Sullivan TE, Johnson LR, Kang HH, Sun JC. BNIP3- and BNIPL-mediated mitophagy promotes the generation of natural killer cell memory. Immunity. 2015;43(2):331–42.CrossRefPubMedPubMedCentral

66.

Singh R, Kaushik S, Wang Y, Xiang Y, Novak I, Komatsu M, et al. Autophagy regulates lipid metabolism. Nature. 2009;458(7242):1131–5. https://doi.org/10.1038/nature07976.CrossRefPubMedPubMedCentral

67.

Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4⁺ CD25⁺ regulatory T cells. Nat Immunol. 2003;4(4):330–6.CrossRefPubMed

68.

Apostolidis SA, Rodriguez-Rodriguez N, Suarez-Fueyo A, Dioufa N, Ozcan E, Crispin JC, et al. Protein phosphatase 2A is requisite for the function of regulatory T cells. Nat Immunol. 2016;17(5):556–64. https://doi.org/10.1038/ni.3390.CrossRefPubMedPubMedCentral

69.

Lanna A, Henson SM, Escors D, Akbar AN. AMPK-TAB1 activated p38 drives human T cell senescence. Nat Immunol. 2014;15(10):965–72.CrossRefPubMedPubMedCentral

70.

Frumento G, Rotondo R, Tonetti M, Damonte G, Benatti U, Ferrara GB. Tryptophan-derived catabolites are responsible for inhibition of T and natural killer cell proliferation induced by indoleamine 2,3-dioxygenase. J Exp Med. 2002;196(4):459–68.CrossRefPubMedPubMedCentral

71.

Eleftheriadis T, Pissas G, Antoniadi G, Liakopoulos V, Stefanidis I. Indoleamine 2,3-dioxygenase depletes tryptophan, activates general control non-derepressible 2 kinase and down-regulates key enzymes involved in fatty acid synthesis in primary human CD4⁺ T cells. Immunology. 2015;146(2):292–300.CrossRefPubMedPubMedCentral

72.

Eleftheriadis T, Pissas G, Yiannaki E, Markala D, Arampatzis S, Antoniadi G, et al. Inhibition of indoleamine 2,3-dioxygenase in mixed lymphocyte reaction affects glucose influx and enzymes involved in aerobic glycolysis and glutaminolysis in alloreactive T-cells. Hum Immunol. 2013;74(12):1501–9.CrossRefPubMed

73.

Gianchecchi E, Delfino DV, Fierabracci A. Recent insights into the role of the PD-1/PD-L1 pathway in immunological tolerance and autoimmunity. Autoimmun Rev. 2013;12(11):1091–100. https://doi.org/10.1016/j.autrev.2013.05.003.CrossRefPubMed

74.

Barber DL, Wherry EJ, Masopust D, Zhu B, Allison JP, Sharpe AH, et al. Restoring function in exhausted CD8 T cells during chronic viral infection. Nature. 2006;439(7077):682–7.CrossRefPubMed

75.

Zhang L, Gajewski TF, Kline J. PD-1/PD-L1 interactions inhibit antitumor immune responses in a murine acute myeloid leukemia model. Blood. 2009;114(8):1545–52. https://doi.org/10.1182/blood-2009-03-206672.CrossRefPubMedPubMedCentral

76.

Patsoukis N, Bardhan K, Chatterjee P, Sari D, Liu B, Bell LN, et al. PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation. Nat Commun. 2015;26(6):6692.CrossRef

77.

Muller-Durovic B, Lanna A, Polaco Covre L, Mills RS, Henson SM, Akbar AN. Killer cell lectin-like receptor G1 inhibits NK cell function through activation of adenosine 5′-monophosphate-activated protein kinase. J Immunol. 2016;197(7):2891–9.CrossRefPubMedPubMedCentral

78.

Kim KY, Kim JK, Han SH, Lim JS, Kim KI, Cho DH, et al. Adiponectin is a negative regulator of NK cell cytotoxicity. J Immunol. 2006;176(10):5958–64.CrossRefPubMed

79.

Viel S, Marçais A, Guimaraes FS, Loftus R, Rabilloud J, Grau M, et al. TGF-β inhibits the activation and functions of NK cells by repressing the mTOR pathway. Sci Signal. 2016;9(415):ra19.CrossRefPubMed

80.

Brand A, Singer K, Koehl GE, Kolitzus M, Schoenhammer G, Thiel A, et al. LDHA-associated lactic acid production blunts tumor immunosurveillance by T and NK cells. Cell Metab. 2016;24(5):657–71.CrossRefPubMed

81.

Della Chiesa M, Carlomagno S, Frumento G, Balsamo M, Cantoni C, Conte R, et al. The tryptophan catabolite L-kynurenine inhibits the surface expression of NKp46- and NKG2D-activating receptors and regulates NK-cell function. Blood. 2006;108(13):4118–25.CrossRefPubMed

82.

Beldi-Ferchiou A, Lambert M, Dogniaux S, Vély F, Vivier E, Olive D, et al. PD-1 mediates functional exhaustion of activated NK cells in patients with Kaposi sarcoma. Oncotarget. 2016;7(45):72961–77. https://doi.org/10.18632/oncotarget.12150.CrossRefPubMedPubMedCentral

83.

Briercheck EL, Trotta R, Chen L, Hartlage AS, Cole JP, Cole TD, et al. PTEN is a negative regulator of NK cell cytolytic function. J Immunol. 2015;194(4):1832–40. https://doi.org/10.4049/jimmunol.1401224.CrossRefPubMedPubMedCentral

84.

Ali AK, Nandagopal N, Lee SH. IL-15–PI3K–AKT–mTOR: a critical pathway in the life journey of natural killer cells. Front Immunol. 2015;6:335. https://doi.org/10.3389/fimmu.2015.00355.CrossRef

85.

Trotta R, Ciarlariello D, Dal Col J, Mao H, Chen L, Briercheck E, et al. The PP2A inhibitor SET regulates granzyme B expression in human natural killer cells. Blood. 2011;117(8):2378–84. https://doi.org/10.1182/blood-2010-05-285130.CrossRefPubMedPubMedCentral

86.

Trotta R, Ciarlariello D, Dal Col J, Allard J, Neviani P, Santhanam R, et al. The PP2A inhibitor SET regulates natural killer cell IFN-gamma production. J Exp Med. 2007;204(10):2397–405.CrossRefPubMedPubMedCentral

87.

Kawada M, Kawatsu M, Masuda T, Ohba S, Amemiya M, Kohama T, et al. Specific inhibitors of protein phosphatase 2A inhibit tumor metastasis through augmentation of natural killer cells. Int Immunopharmacol. 2003;3(2):179–88.CrossRefPubMed

88.

Fischer HJ, Sie C, Schumann E, Witte AK, Dressel R, van den Brandt J, et al. The insulin receptor plays a critical role in T cell function and adaptive immunity. J Immunol. 2017;198(5):1910–20. https://doi.org/10.4049/jimmunol.1601011.CrossRefPubMed

89.

Maratou E, Dimitriadis G, Kollias A, Boutati E, Lambadiari V, Mitrou P, et al. Glucose transporter expression on the plasma membrane of resting and activated white blood cells. Eur J Clin Investig. 2007;37(4):282–90. https://doi.org/10.1111/j.1365-2362.2007.01786.x.CrossRef

90.

Amer J, Salhab A, Noureddin M, Doron S, Abu-Tair L, Ghantous R, et al. Insulin signaling as a potential natural killer cell checkpoint in fatty liver disease. Hepatol Commun. 2018;2(3):285–98. https://doi.org/10.1002/hep4.1146.CrossRefPubMedPubMedCentral

91.

Li J, Kim SG, Blenis J. Rapamycin: one drug, many effects. Cell Metab. 2014;19(3):373–9. https://doi.org/10.1016/j.cmet.2014.01.001.CrossRefPubMedPubMedCentral

92.

Rao RR, Li Q, Odunsi K, Shrikant PA. The mTOR kinase determines effector versus memory CD8⁺ T cell fate by regulating the expression of transcription factors T-bet and eomesodermin. Immunity. 2010;32(1):67–78. https://doi.org/10.1016/j.immuni.2009.10.010.CrossRefPubMedPubMedCentral

93.

Natali A, Ferrannini E. Effects of metformin and thiazolidinediones on suppression of hepatic glucose production and stimulation of glucose uptake in type 2 diabetes: a systematic review. Diabetologia. 2006;49(3):434–41. https://doi.org/10.1007/s00125-006-0141-7.CrossRefPubMed

94.

Gualdoni GA, Mayer KA, Goschl L, Boucheron N, Ellmeier W, Zlabinger GJ. The AMP analog AICAR modulates the Treg/Th17 axis through enhancement of fatty acid oxidation. FASEB J. 2016;30(11):3800–9. https://doi.org/10.1096/fj.201600522R.CrossRefPubMed

95.

Fullerton MD, Galic S, Marcinko K, Sikkema S, Pulinilkunnil T, Chen ZP, et al. Single phosphorylation sites in Acc1 and Acc2 regulate lipid homeostasis and the insulin-sensitizing effects of metformin. Nat Med. 2013;19(12):1649–54. https://doi.org/10.1038/nm.3372.CrossRefPubMedPubMedCentral

96.

Park MJ, Lee SY, Moon SJ, Son HJ, Lee SH, Kim EK, et al. Metformin attenuates graft-versus-host disease via restricting mammalian target of rapamycin/signal transducer and activator of transcription 3 and promoting adenosine monophosphate-activated protein kinase-autophagy for the balance between T helper 17 and Tregs. Transl Res J Lab Clin Med. 2016;173:115–30. https://doi.org/10.1016/j.trsl.2016.03.006.CrossRef

Titel: Immunometabolism of T cells and NK cells: metabolic control of effector and regulatory function
verfasst von: Sophie M. Poznanski
Nicole G. Barra
Ali A. Ashkar
Jonathan D. Schertzer
Publikationsdatum: 31.07.2018
Verlag: Springer International Publishing
Erschienen in: Inflammation Research / Ausgabe 10/2018
Print ISSN: 1023-3830
Elektronische ISSN: 1420-908X
DOI: https://doi.org/10.1007/s00011-018-1174-3

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26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

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