Hypoxia and hypoxia-inducible factors as regulators of T cell development, differentiation, and function

Immunologic Research

Volumn 55, Issue 1-3, 2013, Pages 58-70

  McNamee, Eóin N ^a   Korns Johnson, Darlynn ^a,b   Homann, Dirk ^a,b   Clambey, Eric T ^a  

^a UNIVERSITY OF COLORADO SCHOOL OF MEDICINE   (United States)

^b DEPARTMENT OF MEDICINE   (United States)

Author keywords

Hypoxia; Hypoxia inducible factor; Metabolism; Oxygen; T cell

Indexed keywords

HYPOXIA INDUCIBLE FACTOR 1ALPHA; HYPOXIA INDUCIBLE FACTOR 2ALPHA;

ARTICLE; CELL DIFFERENTIATION; CELL FUNCTION; CELL MATURATION; HUMAN; HYPOXIA; NONHUMAN; OXYGEN CONSUMPTION; OXYGEN SENSING; OXYGEN SUPPLY; OXYGEN TENSION; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; T LYMPHOCYTE; TH17 CELL;

ANIMALS; ANOXIA; BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS; CELL DIFFERENTIATION; HUMANS; OXYGEN; T-LYMPHOCYTES;

EID: 84876741058     PISSN: 0257277X     EISSN: 15590755     Source Type: Journal    
DOI: 10.1007/s12026-012-8349-8     Document Type: Article

References (128)

1. Taylor CT, McElwain JC. Ancient atmospheres and the evolution of oxygen sensing via the hypoxia-inducible factor in metazoans. Physiology (Bethesda). 2010;25(5):272-9.
2. Semenza GL. Oxygen sensing, homeostasis, and disease. N Engl J Med. 2011;365(6):537-47.
3. Leach RM, Treacher DF. Oxygen transport-2. Tissue hypoxia. BMJ. 1998;317(7169):1370-3.
4. Jiang BH, Semenza GL, Bauer C, Marti HH. Hypoxia-inducible factor 1 levels vary exponentially over a physiologically relevant range of O2 tension. Am J Physiol. 1996;271(4 Pt 1):C1172-80.
5. Jones RG, Thompson CB. Revving the engine: signal transduction fuels T cell activation. Immunity. 2007;27(2):173-8.
6. Colgan SP, Taylor CT. Hypoxia: an alarm signal during intestinal inflammation. Nat Rev Gastroenterol Hepatol. 2010;7(5):281-7.
7. Braun RD, Lanzen JL, Snyder SA, Dewhirst MW. Comparison of tumor and normal tissue oxygen tension measurements using OxyLite or microelectrodes in rodents. Am J Physiol Heart Circ Physiol. 2001;280(6):H2533-44.
8. Caldwell CC, Kojima H, Lukashev D, Armstrong J, Farber M, Apasov SG, et al. Differential effects of physiologically relevant hypoxic conditions on T lymphocyte development and effector functions. J Immunol. 2001;167(11):6140-9.
9. Varghese AJ, Gulyas S, Mohindra JK. Hypoxia-dependent reduction of 1-(2-nitro-1-imidazolyl)-3-methoxy-2-propanol by Chinese hamster ovary cells and KHT tumor cells in vitro and in vivo. Cancer Res. 1976;36(10):3761-5.
10. Thiel M, Caldwell CC, Kreth S, Kuboki S, Chen P, Smith P, et al. Targeted deletion of HIF-1alpha gene in T cells prevents their inhibition in hypoxic inflamed tissues and improves septic mice survival. PLoS ONE. 2007;2(9):e853.
11. Parmar K, Mauch P, Vergilio JA, Sackstein R, Down JD. Distribution of hematopoietic stem cells in the bone marrow according to regional hypoxia. Proc Natl Acad Sci USA. 2007;104(13):5431-6.
12. Karhausen J, Furuta GT, Tomaszewski JE, Johnson RS, Colgan SP, Haase VH. Epithelial hypoxia-inducible factor-1 is protective in murine experimental colitis. J Clin Invest. 2004;114(8):1098-106.
13. Boutin AT, Weidemann A, Fu Z, Mesropian L, Gradin K, Jamora C, et al. Epidermal sensing of oxygen is essential for systemic hypoxic response. Cell. 2008;133(2):223-34.
14. Takubo K, Goda N, Yamada W, Iriuchishima H, Ikeda E, Kubota Y, et al. Regulation of the HIF-1alpha level is essential for hematopoietic stem cells. Cell Stem Cell. 2010;7(3):391-402.
15. Eltzschig HK, Carmeliet P. Hypoxia and inflammation. N Engl J Med. 2011;364(7):656-65.
16. Via LE, Lin PL, Ray SM, Carrillo J, Allen SS, Eum SY, et al. Tuberculous granulomas are hypoxic in guinea pigs, rabbits, and nonhuman primates. Infect Immun. 2008;76(6):2333-40.
17. Semenza GL, Prabhakar NR. HIF-1-dependent respiratory, cardiovascular, and redox responses to chronic intermittent hypoxia. Antioxid Redox Signal. 2007;9(9):1391-6.
18. Andrikopoulou E, Zhang X, Sebastian R, Marti G, Liu L, Milner SM, et al. Current Insights into the role of HIF-1 in cutaneous wound healing. Curr Mol Med. 2011;11(3):218-35.
19. Bertout JA, Patel SA, Simon MC. The impact of O2 availability on human cancer. Nat Rev Cancer. 2008;8(12):967-75.
20. Carmeliet P, Jain RK. Principles and mechanisms of vessel normalization for cancer and other angiogenic diseases. Nat Rev Drug Discov. 2011;10(6):417-27.
21. Eltzschig HK, Eckle T. Ischemia and reperfusion - from mechanism to translation. Nat Med. 2011;17(11):1391-401.
22. Ye J. Emerging role of adipose tissue hypoxia in obesity and insulin resistance. Int J Obes (Lond). 2009;33(1):54-66.
23. Sitkovsky M, Lukashev D. Regulation of immune cells by local-tissue oxygen tension: HIF1 alpha and adenosine receptors. Nat Rev Immunol. 2005;5(9):712-21.
24. Noman MZ, Messai Y, Carre T, Akalay I, Meron M, Janji B, et al. Microenvironmental hypoxia orchestrating the cell stroma cross talk, tumor progression and antitumor response. Crit Rev Immunol. 2011;31(5):357-77.
25. Caldwell CC, Tschoep J, Lentsch AB. Lymphocyte function during hepatic ischemia/reperfusion injury. J Leukoc Biol. 2007;82(3):457-64.
26. Huang Y, Rabb H, Womer KL. Ischemia-reperfusion and immediate T cell responses. Cell Immunol. 2007;248(1):4-11.
27. Rausch ME, Weisberg S, Vardhana P, Tortoriello DV. Obesity in C57BL/6J mice is characterized by adipose tissue hypoxia and cytotoxic T-cell infiltration. Int J Obes (Lond). 2008;32(3):451-63.
28. Nishimura S, Manabe I, Nagasaki M, Eto K, Yamashita H, Ohsugi M, et al. CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat Med. 2009;15(8):914-20.
29. Feuerer M, Herrero L, Cipolletta D, Naaz A, Wong J, Nayer A, et al. Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med. 2009;15(8):930-9.
30. Winer S, Chan Y, Paltser G, Truong D, Tsui H, Bahrami J, et al. Normalization of obesity-associated insulin resistance through immunotherapy. Nat Med. 2009;15(8):921-9.
31. Hangai-Hoger N, Cabrales P, Briceno JC, Tsai AG, Intaglietta M. Microlymphatic and tissue oxygen tension in the rat mesentery. Am J Physiol Heart Circ Physiol. 2004;286(3):H878-83.
32. Ohhashi T, Mizuno R, Ikomi F, Kawai Y. Current topics of physiology and pharmacology in the lymphatic system. Pharmacol Ther. 2005;105(2):165-88.
33. Hangai-Hoger N, Tsai AG, Cabrales P, Intaglietta M. Terminal lymphatics: the potential "lethal corner" in the distribution of tissue pO2. Lymphat Res Biol. 2007;5(3):159-68.
34. Higashiyama M, Hokari R, Hozumi H, Kurihara C, Ueda T, Watanabe C, et al. HIF-1 in T cells ameliorated dextran sodium sulfate-induced murine colitis. J Leukoc Biol. 2012;91(6):901-9.
35. Gaber T, Haupl T, Sandig G, Tykwinska K, Fangradt M, Tschirschmann M, et al. Adaptation of human CD4+ T cells to pathophysiological hypoxia: a transcriptome analysis. J Rheumatol. 2009;36(12):2655-69.
36. Semenza GL. Regulation of mammalian O2 homeostasis by hypoxia-inducible factor 1. Annu Rev Cell Dev Biol. 1999;15:551-78.
37. Mole DR, Blancher C, Copley RR, Pollard PJ, Gleadle JM, Ragoussis J, et al. Genome-wide association of hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha DNA binding with expression profiling of hypoxia-inducible transcripts. J Biol Chem. 2009;284(25):16767-75.
38. Schodel J, Oikonomopoulos S, Ragoussis J, Pugh CW, Ratcliffe PJ, Mole DR. High-resolution genome-wide mapping of HIF-binding sites by ChIP-seq. Blood. 2011;117(23):e207-17.
39. Wenger RH, Stiehl DP, Camenisch G. Integration of oxygen signaling at the consensus HRE. Sci STKE. 2005;2005(306):re12.
40. Semenza GL. Regulation of oxygen homeostasis by hypoxia-inducible factor 1. Physiology (Bethesda). 2009;24:97-106.
41. Ivan M, Kondo K, Yang H, Kim W, Valiando J, Ohh M, et al. HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. Science. 2001;292(5516):464-8.
42. Yu F, White SB, Zhao Q, Lee FS. HIF-1alpha binding to VHL is regulated by stimulus-sensitive proline hydroxylation. Proc Natl Acad Sci USA. 2001;98(17):9630-5.
43. Jaakkola P, Mole DR, Tian YM, Wilson MI, Gielbert J, Gaskell SJ, et al. Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science. 2001;292(5516):468-72.
44. Kaelin WG Jr, Ratcliffe PJ. Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Mol Cell. 2008;30(4):393-402.
45. Mahon PC, Hirota K, Semenza GL. FIH-1: a novel protein that interacts with HIF-1alpha and VHL to mediate repression of HIF-1 transcriptional activity. Genes Dev. 2001;15(20):2675-86.
46. Lando D, Peet DJ, Whelan DA, Gorman JJ, Whitelaw ML. Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch. Science. 2002;295(5556):858-61.
47. Tian H, McKnight SL, Russell DW. Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells. Genes Dev. 1997;11(1):72-82.
48. Rankin EB, Biju MP, Liu Q, Unger TL, Rha J, Johnson RS, et al. Hypoxia-inducible factor-2 (HIF-2) regulates hepatic erythropoietin in vivo. J Clin Invest. 2007;117(4):1068-77.
49. Gruber M, Hu CJ, Johnson RS, Brown EJ, Keith B, Simon MC. Acute postnatal ablation of Hif-2alpha results in anemia. Proc Natl Acad Sci USA. 2007;104(7):2301-6.
50. Takeda N, O'Dea EL, Doedens A, Kim JW, Weidemann A, Stockmann C, et al. Differential activation and antagonistic function of HIF-{alpha} isoforms in macrophages are essential for NO homeostasis. Genes Dev. 2010;24(5):491-501.
51. Imtiyaz HZ, Williams EP, Hickey MM, Patel SA, Durham AC, Yuan LJ, et al. Hypoxia-inducible factor 2alpha regulates macrophage function in mouse models of acute and tumor inflammation. J Clin Invest. 2010;120(8):2699-714.
52. Keith B, Johnson RS, Simon MC. HIF1alpha and HIF2alpha: sibling rivalry in hypoxic tumour growth and progression. Nat Rev Cancer. 2011;12(1):9-22.
53. Cummins EP, Taylor CT. Hypoxia-responsive transcription factors. Pflugers Arch. 2005;450(6):363-71.
54. Taylor CT, Cummins EP. The role of NF-kappaB in hypoxia-induced gene expression. Ann N Y Acad Sci. 2009;1177:178-84.
55. Rius J, Guma M, Schachtrup C, Akassoglou K, Zinkernagel AS, Nizet V, et al. NF-kappaB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1alpha. Nature. 2008;453(7196):807-11.
56. Pocock R. Invited review: decoding the microRNA response to hypoxia. Pflugers Arch. 2011;461(3):307-15.
57. Watson JA, Watson CJ, McCann A, Baugh J. Epigenetics, the epicenter of the hypoxic response. Epigenetics. 2010;5(4):293-6.
58. Taylor CT. Mitochondria and cellular oxygen sensing in the HIF pathway. Biochem J. 2008;409(1):19-26.
59. Hamanaka RB, Chandel NS. Mitochondrial reactive oxygen species regulate hypoxic signaling. Curr Opin Cell Biol. 2009;21(6):894-9.
60. Waypa GB, Schumacker PT. Hypoxia-induced changes in pulmonary and systemic vascular resistance: where is the O2 sensor? Respir Physiol Neurobiol. 2010;174(3):201-11.
61. Boulahbel H, Duran RV, Gottlieb E. Prolyl hydroxylases as regulators of cell metabolism. Biochem Soc Trans. 2009;37(Pt 1):291-4.
62. Wang GL, Semenza GL. Desferrioxamine induces erythropoietin gene expression and hypoxia-inducible factor 1 DNA-binding activity: implications for models of hypoxia signal transduction. Blood. 1993;82(12):3610-5.
63. Hartmann H, Eltzschig HK, Wurz H, Hantke K, Rakin A, Yazdi AS, et al. Hypoxia-independent activation of HIF-1 by enterobacteriaceae and their siderophores. Gastroenterology. 2008;134(3):756-67.
64. Maxwell PH, Pugh CW, Ratcliffe PJ. Inducible operation of the erythropoietin 3′ enhancer in multiple cell lines: evidence for a widespread oxygen-sensing mechanism. Proc Natl Acad Sci USA. 1993;90(6):2423-7.
65. Isaacs JS, Jung YJ, Mole DR, Lee S, Torres-Cabala C, Chung YL, et al. HIF overexpression correlates with biallelic loss of fumarate hydratase in renal cancer: novel role of fumarate in regulation of HIF stability. Cancer Cell. 2005;8(2):143-53.
66. Selak MA, Armour SM, MacKenzie ED, Boulahbel H, Watson DG, Mansfield KD, et al. Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase. Cancer Cell. 2005;7(1):77-85.
67. Pan Y, Mansfield KD, Bertozzi CC, Rudenko V, Chan DA, Giaccia AJ, et al. Multiple factors affecting cellular redox status and energy metabolism modulate hypoxia-inducible factor prolyl hydroxylase activity in vivo and in vitro. Mol Cell Biol. 2007;27(3):912-25.
68. Koivunen P, Hirsila M, Remes AM, Hassinen IE, Kivirikko KI, Myllyharju J. Inhibition of hypoxia-inducible factor (HIF) hydroxylases by citric acid cycle intermediates: possible links between cell metabolism and stabilization of HIF. J Biol Chem. 2007;282(7):4524-32.
69. Nakamura H, Makino Y, Okamoto K, Poellinger L, Ohnuma K, Morimoto C, et al. TCR engagement increases hypoxia-inducible factor-1 alpha protein synthesis via rapamycin-sensitive pathway under hypoxic conditions in human peripheral T cells. J Immunol. 2005;174(12):7592-9.
70. Lukashev D, Sitkovsky M. Preferential expression of the novel alternative isoform I.3 of hypoxia-inducible factor 1alpha in activated human T lymphocytes. Hum Immunol. 2008;69(7):421-5.
71. Dang EV, Barbi J, Yang HY, Jinasena D, Yu H, Zheng Y, et al. Control of T(H)17/T(reg) balance by hypoxia-inducible factor 1. Cell. 2011;146(5):772-84.
72. Larbi A, Zelba H, Goldeck D, Pawelec G. Induction of HIF-1alpha and the glycolytic pathway alters apoptotic and differentiation profiles of activated human T cells. J Leukoc Biol. 2010;87(2):265-73.
73. Tripmacher R, Gaber T, Dziurla R, Haupl T, Erekul K, Grutzkau A, et al. Human CD4(+) T cells maintain specific functions even under conditions of extremely restricted ATP production. Eur J Immunol. 2008;38(6):1631-42.
74. Atkuri KR, Herzenberg LA, Herzenberg LA. Culturing at atmospheric oxygen levels impacts lymphocyte function. Proc Natl Acad Sci USA. 2005;102(10):3756-9.
75. Atkuri KR, Herzenberg LA, Niemi AK, Cowan T, Herzenberg LA. Importance of culturing primary lymphocytes at physiological oxygen levels. Proc Natl Acad Sci USA. 2007;104(11):4547-52.
76. Goda N, Ryan HE, Khadivi B, McNulty W, Rickert RC, Johnson RS. Hypoxia-inducible factor 1alpha is essential for cell cycle arrest during hypoxia. Mol Cell Biol. 2003;23(1):359-69.
77. Hubbi ME, Luo W, Baek JH, Semenza GL. MCM proteins are negative regulators of hypoxia-inducible factor 1. Mol Cell. 2011;42(5):700-12.
78. Robbins JR, Lee SM, Filipovich AH, Szigligeti P, Neumeier L, Petrovic M, et al. Hypoxia modulates early events in T cell receptor-mediated activation in human T lymphocytes via Kv1.3 channels. J Physiol. 2005;564(Pt 1):131-43.
79. Makino Y, Nakamura H, Ikeda E, Ohnuma K, Yamauchi K, Yabe Y, et al. Hypoxia-inducible factor regulates survival of antigen receptor-driven T cells. J Immunol. 2003;171(12):6534-40.
80. Guo J, Lu W, Shimoda LA, Semenza GL, Georas SN. Enhanced interferon-gamma gene expression in T Cells and reduced ovalbumin-dependent lung eosinophilia in hypoxia-inducible factor-1-alpha-deficient mice. Int Arch Allergy Immunol. 2009;149(2):98-102.
81. Ikejiri A, Nagai S, Goda N, Kurebayashi Y, Osada-Oka M, Takubo K, et al. Dynamic regulation of Th17 differentiation by oxygen concentrations. Int Immunol. 2012;24(3):137-46.
82. Nizet V, Johnson RS. Interdependence of hypoxic and innate immune responses. Nat Rev Immunol. 2009;9(9):609-17.
83. Facciabene A, Peng X, Hagemann IS, Balint K, Barchetti A, Wang LP, et al. Tumour hypoxia promotes tolerance and angiogenesis via CCL28 and T(reg) cells. Nature. 2011;475(7355):226-30.
84. Doedens AL, Stockmann C, Rubinstein MP, Liao D, Zhang N, DeNardo DG, et al. Macrophage expression of hypoxia-inducible factor-1 alpha suppresses T-cell function and promotes tumor progression. Cancer Res. 2010;70(19):7465-75.
85. Corzo CA, Condamine T, Lu L, Cotter MJ, Youn JI, Cheng P, et al. HIF-1alpha regulates function and differentiation of myeloid-derived suppressor cells in the tumor microenvironment. J Exp Med. 2010;207(11):2439-53.
86. Noman MZ, Buart S, Van Pelt J, Richon C, Hasmim M, Leleu N, et al. The cooperative induction of hypoxia-inducible factor-1 alpha and STAT3 during hypoxia induced an impairment of tumor susceptibility to CTL-mediated cell lysis. J Immunol. 2009;182(6):3510-21.
87. Noman MZ, Janji B, Kaminska B, Van Moer K, Pierson S, Przanowski P, et al. Blocking hypoxia-induced autophagy in tumors restores cytotoxic T-cell activity and promotes regression. Cancer Res. 2011;71(18):5976-86.
88. Fischer K, Hoffmann P, Voelkl S, Meidenbauer N, Ammer J, Edinger M, et al. Inhibitory effect of tumor cell-derived lactic acid on human T cells. Blood. 2007;109(9):3812-9.
89. Ostroukhova M, Goplen N, Karim MZ, Michalec L, Guo L, Liang Q, et al. The role of low-level lactate production in airway inflammation in asthma. Am J Physiol Lung Cell Mol Physiol. 2012;302(3):L300-7.
90. Doedens A, Johnson RS. Transgenic models to understand hypoxia-inducible factor function. Meth Enzymol. 2007;435:87-105.
91. Biju MP, Neumann AK, Bensinger SJ, Johnson RS, Turka LA, Haase VH. Vhlh gene deletion induces Hif-1-mediated cell death in thymocytes. Mol Cell Biol. 2004;24(20):9038-47.
92. Neumann AK, Yang J, Biju MP, Joseph SK, Johnson RS, Haase VH, et al. Hypoxia inducible factor 1 alpha regulates T cell receptor signal transduction. Proc Natl Acad Sci USA. 2005;102(47):17071-6.
93. Lukashev D, Klebanov B, Kojima H, Grinberg A, Ohta A, Berenfeld L, et al. Cutting edge: hypoxia-inducible factor 1alpha and its activation-inducible short isoform I.1 negatively regulate functions of CD4+ and CD8+ T lymphocytes. J Immunol. 2006;177(8):4962-5.
94. Kurobe H, Urata M, Ueno M, Ueki M, Ono S, Izawa-Ishizawa Y, et al. Role of hypoxia-inducible factor 1alpha in T cells as a negative regulator in development of vascular remodeling. Arterioscler Thromb Vasc Biol. 2010;30(2):210-7.
95. Ben-Shoshan J, Maysel-Auslender S, Mor A, Keren G, George J. Hypoxia controls CD4+ CD25+ regulatory T-cell homeostasis via hypoxia-inducible factor-1alpha. Eur J Immunol. 2008;38(9):2412-8.
96. Seder RA, Ahmed R. Similarities and differences in CD4+ and CD8+ effector and memory T cell generation. Nat Immunol. 2003;4(9):835-42.
97. 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.
98. Zheng Y, Chaudhry A, Kas A, de Roos P, Kim JM, Chu TT, et al. Regulatory T-cell suppressor program co-opts transcription factor IRF4 to control T(H)2 responses. Nature. 2009;458(7236):351-6.
99. Chaudhry A, Rudra D, Treuting P, Samstein RM, Liang Y, Kas A, et al. CD4+ regulatory T cells control TH17 responses in a Stat3-dependent manner. Science. 2009;326(5955):986-91.
100. Koch MA, Tucker-Heard G, Perdue NR, Killebrew JR, Urdahl KB, Campbell DJ. The transcription factor T-bet controls regulatory T cell homeostasis and function during type 1 inflammation. Nat Immunol. 2009;10(6):595-602.
101. Chung Y, Tanaka S, Chu F, Nurieva RI, Martinez GJ, Rawal S, et al. Follicular regulatory T cells expressing Foxp3 and Bcl-6 suppress germinal center reactions. Nat Med. 2011;17(8):983-8.
102. Linterman MA, Pierson W, Lee SK, Kallies A, Kawamoto S, Rayner TF, et al. Foxp3+ follicular regulatory T cells control the germinal center response. Nat Med. 2011;17(8):975-82.
103. Cretney E, Xin A, Shi W, Minnich M, Masson F, Miasari M, et al. The transcription factors Blimp-1 and IRF4 jointly control the differentiation and function of effector regulatory T cells. Nat Immunol. 2011;12(4):304-11.
104. Wang Y, Su MA, Wan YY. An essential role of the transcription factor GATA-3 for the function of regulatory T cells. Immunity. 2011;35(3):337-48.
105. Wohlfert EA, Grainger JR, Bouladoux N, Konkel JE, Oldenhove G, Ribeiro CH, et al. GATA3 controls Foxp3 regulatory T cell fate during inflammation in mice. J Clin Invest. 2011;121(11):4503-15.
106. Pearce EL. Metabolism in T cell activation and differentiation. Curr Opin Immunol. 2010;22(3):314-20.
107. Michalek RD, Rathmell JC. The metabolic life and times of a T-cell. Immunol Rev. 2010;236:190-202.
108. Michalek RD, Gerriets VA, Jacobs SR, Macintyre AN, MacIver 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.
109. 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;36(1):68-78.
110. Semenza GL. Regulation of Metabolism by Hypoxia-Inducible Factor 1. Cold Spring Harb Symp Quant Biol. 2011;76:347-53.
111. 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):871-82.
112. Esser C, Rannug A, Stockinger B. The aryl hydrocarbon receptor in immunity. Trends Immunol. 2009;30(9):447-54.
113. Pot C, Apetoh L, Kuchroo VK. Type 1 regulatory T cells (Tr1) in autoimmunity. Semin Immunol. 2011;23(3):202-8.
114. Glover LE, Irizarry K, Scully M, Campbell EL, Bowers BE, Aherne CM, et al. IFN-gamma attenuates hypoxia-inducible factor (HIF) activity in intestinal epithelial cells through transcriptional repression of HIF-1beta. J Immunol. 2011;186(3):1790-8.
115. Fraisl P, Aragones J, Carmeliet P. Inhibition of oxygen sensors as a therapeutic strategy for ischaemic and inflammatory disease. Nat Rev Drug Discov. 2009;8(2):139-52.
116. Okumura CY, Hollands A, Tran DN, Olson J, Dahesh S, von Kockritz-Blickwede M et al. A new pharmacological agent (AKB-4924) stabilizes hypoxia inducible factor-1 (HIF-1) and increases skin innate defenses against bacterial infection. J Mol Med (Berl). 2012;90(9):1079-89.
117. Cummins EP, Seeballuck F, Keely SJ, Mangan NE, Callanan JJ, Fallon PG, et al. The hydroxylase inhibitor dimethyloxalylglycine is protective in a murine model of colitis. Gastroenterology. 2008;134(1):156-65.
118. Robinson A, Keely S, Karhausen J, Gerich ME, Furuta GT, Colgan SP. Mucosal protection by hypoxia-inducible factor prolyl hydroxylase inhibition. Gastroenterology. 2008;134(1):145-55.
119. Hindryckx P, De Vos M, Jacques P, Ferdinande L, Peeters H, Olievier K, et al. Hydroxylase inhibition abrogates TNF-alpha-induced intestinal epithelial damage by hypoxia-inducible factor-1-dependent repression of FADD. J Immunol. 2010;185(10):6306-16.
120. Hams E, Saunders SP, Cummins EP, O'Connor A, Tambuwala MT, Gallagher WM, et al. The hydroxylase inhibitor dimethyloxallyl glycine attenuates endotoxic shock via alternative activation of macrophages and IL-10 production by B1 cells. Shock. 2011;36(3):295-302.
121. Bernhardt WM, Wiesener MS, Scigalla P, Chou J, Schmieder RE, Gunzler V, et al. Inhibition of prolyl hydroxylases increases erythropoietin production in ESRD. J Am Soc Nephrol. 2010;21(12):2151-6.
122. Cummins EP, Berra E, Comerford KM, Ginouves A, Fitzgerald KT, Seeballuck F, et al. Prolyl hydroxylase-1 negatively regulates IkappaB kinase-beta, giving insight into hypoxia-induced NFkappaB activity. Proc Natl Acad Sci USA. 2006;103(48):18154-9.
123. Semenza GL. HIF-1 inhibitors for cancer therapy: from gene expression to drug discovery. Curr Pharm Des. 2009;15(33):3839-43.
124. Stravopodis DJ, Margaritis LH, Voutsinas GE. Drug-mediated targeted disruption of multiple protein activities through functional inhibition of the Hsp90 chaperone complex. Curr Med Chem. 2007;14(29):3122-38.
125. Zhang H, Qian DZ, Tan YS, Lee K, Gao P, Ren YR, et al. Digoxin and other cardiac glycosides inhibit HIF-1alpha synthesis and block tumor growth. Proc Natl Acad Sci USA. 2008;105(50):19579-86.
126. Lee K, Zhang H, Qian DZ, Rey S, Liu JO, Semenza GL. Acriflavine inhibits HIF-1 dimerization, tumor growth, and vascularization. Proc Natl Acad Sci USA. 2009;106(42):17910-5.
127. Wilczynski J, Duechler M, Czyz M. Targeting NF-kappaB and HIF-1 pathways for the treatment of cancer: part II. Arch Immunol Ther Exp (Warsz). 2011;59(4):301-7.
128. Clambey ET, McNamee EN, Westrich JA, Glover LE, Campbell EL, Jedlicka P, et al. Hif-1 alpha dependent induction of FoxP3 drives regulatory T cell abundance and function during inflammatory hypoxia of the mucosa. Proc Natl Acad Sci USA. In press.