Amino acid catabolism: A pivotal regulator of innate and adaptive immunity

Immunological Reviews

Volumn 249, Issue 1, 2012, Pages 135-157

  Mcgaha, Tracy L ^a   Huang, Lei ^a   Lemos, Henrique ^a   Metz, Richard ^b   Mautino, Mario ^b   Prendergast, George C ^c   Mellor, Andrew L ^a  

^a MEDICAL COLLEGE OF GEORGIA   (United States)

^b New Link Genetics   (United States)

^c LANKENAU INSTITUTE FOR MEDICAL RESEARCH   (United States)

Author keywords

AHR; D 1MT; eif2ak4; IDO; mTOR; tolerance

Indexed keywords

AMINO ACID; ARGINASE; ARGININE; INDOLEAMINE 2,3 DIOXYGENASE; INDUCIBLE NITRIC OXIDE SYNTHASE; MAMMALIAN TARGET OF RAPAMYCIN; TRYPTOPHAN; TRYPTOPHAN 2,3 DIOXYGENASE;

ADAPTIVE IMMUNITY; ANTIGEN PRESENTING CELL; ARTICLE; AUTOIMMUNITY; BACTERIAL INFECTION; CARCINOGENESIS; CATABOLISM; CELL SURVIVAL; GENE EXPRESSION REGULATION; GENE FUNCTION; GENETIC MANIPULATION; HOMEOSTASIS; HUMAN; IMMUNOCOMPETENT CELL; IMMUNOLOGICAL TOLERANCE; IMMUNOREGULATION; INFLAMMATION; INNATE IMMUNITY; LYMPHOCYTE FUNCTION; MOLECULAR GENETICS; NONHUMAN; OXIDATION; PREGNANCY; PRIORITY JOURNAL; PROTEIN EXPRESSION; REGULATORY MECHANISM; SIGNAL TRANSDUCTION;

ADAPTIVE IMMUNITY; AMINO ACIDS; ANIMALS; HUMANS; IMMUNITY, INNATE; INDOLEAMINE-PYRROLE 2,3,-DIOXYGENASE; PROTEIN-SERINE-THREONINE KINASES; SELF TOLERANCE; TOR SERINE-THREONINE KINASES;

EID: 84865296997     PISSN: 01052896     EISSN: 1600065X     Source Type: Journal    
DOI: 10.1111/j.1600-065X.2012.01149.x     Document Type: Article

References (189)

1. Ball HJ, Yuasa HJ, Austin CJ, Weiser S, Hunt NH. Indoleamine 2, 3-dioxygenase-2; a new enzyme in the kynurenine pathway. Int J Biochem Cell Biol 2009;41:467-471.
2. Metz R, Duhadaway JB, Kamasani U, Laury-Kleintop L, Muller AJ, Prendergast GC. Novel tryptophan catabolic enzyme IDO2 is the preferred biochemical target of the antitumor indoleamine 2, 3-dioxygenase inhibitory compound D-1-methyl-tryptophan. Cancer Res 2007;67:7082-7087.
3. Croitoru-Lamoury J, et al. Interferon-gamma regulates the proliferation and differentiation of mesenchymal stem cells via activation of indoleamine 2, 3 dioxygenase (IDO). PLoS ONE 2011;6:e14698.
4. Suzuki T, Yokouchi K, Kawamichi H, Yamamoto Y, Uda K, Yuasa HJ. Comparison of the sequences of Turbo and Sulculus indoleamine dioxygenase-like myoglobin genes. Gene 2003;308:89-94.
5. Thomas SR, et al. Post-translational regulation of human indoleamine 2, 3-dioxygenase activity by nitric oxide. J Biol Chem 2007;282:23778-23787.
6. Sugimoto H, Oda S, Otsuki T, Hino T, Yoshida T, Shiro Y. Crystal structure of human indoleamine 2, 3-dioxygenase: catalytic mechanism of O2 incorporation by a heme-containing dioxygenase. Proc Natl Acad Sci U S A 2006;103:2611-2616.
7. Chon SY, Hassanain HH, Gupta SL. Cooperative role of interferon regulatory factor 1 and p91 (STAT1) response elements in interferon-gamma-inducible expression of human indoleamine 2, 3-dioxygenase gene. J Biol Chem 1996;271:17247-17252.
8. Konan KV, Taylor MW. Importance of the two interferon-stimulated response element (ISRE) sequences in the regulation of the human indoleamine 2, 3-dioxygenase gene. J Biol Chem 1996;271:19140-19145.
9. Babcock TA, Carlin JM. Transcriptional activation of indoleamine dioxygenase by interleukin 1 and tumor necrosis factor alpha in interferon-treated epithelial cells. Cytokine 2000;12:588-594.
10. Currier AR, Ziegler MH, Riley MM, Babcock TA, Telbis VP, Carlin JM. Tumor necrosis factor-alpha and lipopolysaccharide enhance interferon-induced antichlamydial indoleamine dioxygenase activity independently. J Interferon Cytokine Res 2000;20:369-376.
11. Robinson CM, Shirey KA, Carlin JM. Synergistic transcriptional activation of indoleamine dioxygenase by IFN-gamma and tumor necrosis factor-alpha. J Interferon Cytokine Res 2003;23:413-421.
12. Mellor AL, Baban B, Chandler PR, Manlapat A, Kahler DJ, Munn DH. Cutting Edge: CpG oligonucleotides induce splenic CD19+ dendritic cells to acquire potent indoleamine 2, 3-dioxygenase-dependent T cell regulatory functions via IFN gype 1 signaling. J Immunol 2005;175:5601-5605.
13. Baban B, et al. A minor population of splenic dendritic cells expressing CD19 mediates IDO-dependent T cell suppression via type I IFN signaling following B7 ligation. Int Immunol 2005;17:909-919.
14. Belladonna ML, Orabona C, Grohmann U, Puccetti P. TGF-beta and kynurenines as the key to infectious tolerance. Trends Mol Med 2009;15:41-49.
15. Hassanain HH, Chon SY, Gupta SL. Differential regulation of human indoleamine 2, 3-dioxygenase gene expression by interferons-gamma and -alpha. Analysis of the regulatory region of the gene and identification of an interferon-gamma-inducible DNA-binding factor. J Biol Chem 1993;268:5077-5084.
16. Dai W, Gupta SL. Regulation of indoleamine 2, 3-dioxygenase gene expression in human fibroblasts by interferon-gamma. Upstream control region discriminates between interferon-gamma and interferon-alpha. J Biol Chem 1990;265:19871-19877.
17. Nakajo T, et al. Glutamine is a key regulator for amino acid-controlled cell growth through the mTOR signaling pathway in rat intestinal epithelial cells. Biochem Biophys Res Commun 2005;326:174-180.
18. Pearson JT, Siu S, Meininger DP, Wienkers LC, Rock DA. In vitro modulation of cytochrome P450 reductase supported indoleamine 2, 3-dioxygenase activity by allosteric effectors cytochrome b(5) and methylene blue. Biochemistry 2010;49:2647-2656.
19. Vottero E, et al. Cytochrome b(5) is a major reductant in vivo of human indoleamine 2, 3-dioxygenase expressed in yeast. FEBS Lett 2006;580:2265-2268.
20. Maghzal GJ, Thomas SR, Hunt NH, Stocker R. Cytochrome b5, not superoxide anion radical, is a major reductant of indoleamine 2, 3-dioxygenase in human cells. J Biol Chem 2008;283:12014-12025.
21. Fujigaki H, Seishima M, Saito K. Posttranslational modification of indoleamine 2, 3-dioxygenase. Anal Bioanal Chem 2012;403:1777-1782.
22. Orabona C, et al. SOCS3 drives proteasomal degradation of indoleamine 2, 3-dioxygenase (IDO) and antagonizes IDO-dependent tolerogenesis. Proc Natl Acad Sci U S A 2008;105:20828-20833.
23. Schrocksnadel K, Wirleitner B, Winkler C, Fuchs D. Monitoring tryptophan metabolism in chronic immune activation. Clin Chim Acta 2006;364:82-90.
24. Forouhar F, et al. Molecular insights into substrate recognition and catalysis by tryptophan 2, 3-dioxygenase. Proc Natl Acad Sci U S A 2007;104:473-478.
25. Kanai M, et al. Tryptophan 2, 3-dioxygenase is a key modulator of physiological neurogenesis and anxiety-related behavior in mice. Mol Brain 2009;2:8.
26. Opitz CA, et al. An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor. Nature 2011;478:197-203.
27. Pilotte L, et al. Reversal of tumoral immune resistance by inhibition of tryptophan 2, 3-dioxygenase. Proc Natl Acad Sci U S A 2012;109:2497-2502.
28. Zea AH, et al. L-Arginine modulates CD3zeta expression and T cell function in activated human T lymphocytes. Cell Immunol 2004;232:21-31.
29. Zea AH, et al. Arginase-producing myeloid suppressor cells in renal cell carcinoma patients: a mechanism of tumor evasion. Cancer Res 2005;65:3044-3048.
30. Rodriguez PC, Zea AH, Culotta KS, Zabaleta J, Ochoa JB, Ochoa AC. Regulation of T cell receptor CD3zeta chain expression by L-arginine. J Biol Chem 2002;277:21123-21129.
31. Rodriguez PC, Quiceno DG, Ochoa AC. L-Arginine availability regulates T-lymphocyte cell-cycle progression. Blood 2007;109:1568-1573.
32. Rodriguez PC, Ochoa AC. Arginine regulation by myeloid derived suppressor cells and tolerance in cancer: mechanisms and therapeutic perspectives. Immunol Rev 2008;222:180-191.
33. Rodriguez PC, Zea AH, Ochoa AC. Mechanisms of tumor evasion from the immune response. Cancer Chemother Biol Response Modif 2003;21:351-364.
34. Rodriguez PC, et al. Arginase I production in the tumor microenvironment by mature myeloid cells inhibits T-cell receptor expression and antigen-specific T-cell responses. Cancer Res 2004;64:5839-5849.
35. Rodriguez PC, et al. L-arginine consumption by macrophages modulates the expression of CD3 zeta chain in T lymphocytes. J Immunol 2003;171:1232-1239.
36. Serafini P, Mgebroff S, Noonan K, Borrello I. Myeloid-derived suppressor cells promote cross-tolerance in B-cell lymphoma by expanding regulatory T cells. Cancer Res 2008;68:5439-5449.
37. Serafini P, Borrello I, Bronte V. Myeloid suppressor cells in cancer: recruitment, phenotype, properties, and mechanisms of immune suppression. Semin Cancer Biol 2006;16:53-65.
38. Kropf P, et al. Arginase activity mediates reversible T cell hyporesponsiveness in human pregnancy. Eur J Immunol 2007;37:935-945.
39. Hayashi T, et al. 3-Hydroxyanthranilic acid inhibits PDK1 activation and suppresses experimental asthma by inducing T cell apoptosis. Proc Natl Acad Sci U S A 2007;104:18619-18624.
40. Schmelzle T, Hall MN. TOR, a central controller of cell growth. Cell 2000;103:253-262.
41. Thomson AW, Turnquist HR, Raimondi G. Immunoregulatory functions of mTOR inhibition. Nat Rev Immunol 2009;9:324-337.
42. Powell JD, Pollizzi KN, Heikamp EB, Horton MR. Regulation of immune responses by mTOR. Annu Rev Immunol 2012;30:39-68.
43. Miotto G, Venerando R, Khurana KK, Siliprandi N, Mortimore GE. Control of hepatic proteolysis by leucine and isovaleryl-L-carnitine through a common locus.. J Biol Chem 1992;267:22066-22072.
44. Miotto G, Venerando R, Marin O, Siliprandi N, Mortimore GE. Inhibition of macroautophagy and proteolysis in the isolated rat hepatocyte by a nontransportable derivative of the multiple antigen peptide Leu8-Lys4-Lys2-Lys-beta Ala. J Biol Chem 1994;269:25348-25353.
45. Xu G, Kwon G, Marshall CA, Lin TA, Lawrence JC Jr, McDaniel ML. Branched-chain amino acids are essential in the regulation of PHAS-I and p70 S6 kinase by pancreatic beta-cells. A possible role in protein translation and mitogenic signaling. J Biol Chem 1998;273:28178-28184.
46. Lynch CJ, Fox HL, Vary TC, Jefferson LS, Kimball SR. Regulation of amino acid-sensitive TOR signaling by leucine analogues in adipocytes. J Cell Biochem 2000;77:234-251.
47. Hyde R, Taylor PM, Hundal HS. Amino acid transporters: roles in amino acid sensing and signalling in animal cells. Biochem J 2003;373:1-18.
48. Hara K, Yonezawa K, Weng QP, Kozlowski MT, Belham C, Avruch J. Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism. J Biol Chem 1998;273:14484-14494.
49. Sancak Y, et al. The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science 2008;320:1496-1501.
50. Kim E, Goraksha-Hicks P, Li L, Neufeld TP, Guan KL. Regulation of TORC1 by Rag GTPases in nutrient response. Nat Cell Biol 2008;10:935-945.
51. Han JM, et al. Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway. Cell 2012;149:410-424.
52. Munn DH, et al. GCN2 kinase in T cells mediates proliferative arrest and anergy induction in response to indoleamine 2, 3-dioxygenase. Immunity 2005;22:633-642.
53. Highfill SL, et al. Bone marrow myeloid-derived suppressor cells (MDSCs) inhibit graft-versus-host disease (GVHD) via an arginase-1-dependent mechanism that is up-regulated by interleukin-13. Blood 2010;116:5738-5747.
54. Wek RC, Jiang HY, Anthony TG. Coping with stress: eIF2 kinases and translational control. Biochem Soc Trans 2006;34:7-11.
55. Kilberg MS, Shan J, Su N. ATF4-dependent transcription mediates signaling of amino acid limitation. Trends Endocrinol Metab 2009;20:436-443.
56. Ameri K, Harris AL. Activating transcription factor 4. Int J Biochem Cell Biol 2008;40:14-21.
57. Harding HP, et al. An integrated stress response regulates amino acid metabolism and resistance to oxidative stress. Mol Cell 2003;11:619-633.
58. Gao X, et al. Tsc tumour suppressor proteins antagonize amino-acid-TOR signalling. Nat Cell Biol 2002;4:699-704.
59. Peng W, et al. Surgical stress resistance induced by single amino acid deprivation requires Gcn2 in mice. Sci Transl Med 2012;4:118ra111.
60. Kwon NH, et al. Dual role of methionyl-tRNA synthetase in the regulation of translation and tumor suppressor activity of aminoacyl-tRNA synthetase-interacting multifunctional protein-3. Proc Natl Acad Sci U S A 2011;108:19635-19640.
61. Lee GK, Park HJ, Macleod M, Chandler P, Munn DH, Mellor AL. Tryptophan deprivation sensitizes activated T cells to apoptosis prior to cell division. Immunology 2002;107:452-460.
62. Fallarino F, et al. The combined effects of tryptophan starvation and tryptophan catabolites down-regulate T cell receptor zeta-chain and induce a regulatory phenotype in naive T cells. J Immunol 2006;176:6752-6761.
63. Thornton AM, Piccirillo CA, Shevach EM. Activation requirements for the induction of CD4+ CD25+ T cell suppressor function. Eur J Immunol 2004;34:366-376.
64. Sharma MD, et al. Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2, 3-dioxygenase. J Clin Invest 2007;117:2570-2582.
65. Baban B, et al. IDO activates regulatory T cells and blocks their conversion into Th17-like T cells. J Immunol 2009;183:2475-2483.
66. Sharma MD, et al. Indoleamine 2, 3-dioxygenase controls conversion of Foxp3+ Tregs to TH17-like cells in tumor-draining lymph nodes. Blood 2009;113:6102-6111.
67. Manlapat AK, Kahler DJ, Chandler PR, Munn DH, Mellor AL. Cell-autonomous control of interferon type I expression by indoleamine 2, 3-dioxygenase in regulatory CD19+ dendritic cells. Eur J Immunol 2007;37:1064-1071.
68. Scheu S, Stetson DB, Reinhardt RL, Leber JH, Mohrs M, Locksley RM. Activation of the integrated stress response during T helper cell differentiation. Nat Immunol 2006;7:644-651.
69. Forouzandeh F, Jalili RB, Germain M, Duronio V, Ghahary A. Differential immunosuppressive effect of indoleamine 2, 3-dioxygenase (IDO) on primary human CD4+ and CD8+ T cells. Mol Cell Biochem 2008;309:1-7.
70. Hattori T, Ohoka N, Hayashi H, Onozaki K. C/EBP homologous protein (CHOP) up-regulates IL-6 transcription by trapping negative regulating NF-IL6 isoform. FEBS Lett 2003;541:33-39.
71. Gao H, Schwartz RC. C/EBPzeta (CHOP/Gadd153) is a negative regulator of LPS-induced IL-6 expression in B cells. Mol Immunol 2009;47:390-397.
72. Seymour RL, Ganapathy V, Mellor AL, Munn DH. A high-affinity, tryptophan-selective amino acid transport system in human macrophages. J Leukoc Biol 2006;80:1320-1327.
73. Mellor AL, Munn DH. Tryptophan catabolism and T-cell tolerance: immunosuppression by starvation? Immunol Today 1999;20:469-473.
74. Ravishankar B, et al. Tolerance to apoptotic cells is regulated by indoleamine 2, 3-dioxygenase. Proc Natl Acad Sci U S A 2012;109:3909-3914.
75. Munn DH, et al. Expression of indoleamine 2, 3-dioxygenase by plasmacytoid dendritic cells in tumor-draining lymph nodes. J Clin Invest 2004;114:280-290.
76. Mellor AL, et al. Specific subsets of murine dendritic cells acquire potent T cell regulatory functions following CTLA4-mediated induction of indoleamine 2, 3 dioxygenase. Int Immunol 2004;16:1391-1401.
77. Muller AJ, et al. Chronic inflammation that facilitates tumor progression creates local immune suppression by inducing indoleamine 2, 3 dioxygenase. Proc Natl Acad Sci U S A 2008;105:17073-17078.
78. Johnson BA, Jr, et al. B-lymphoid cells with attributes of dendritic cells regulate T cells via indoleamine 2, 3-dioxygenase. Proc Natl Acad Sci U S A 2010;107:10644-10648.
79. Orabona C, et al. Cutting edge: silencing suppressor of cytokine signaling 3 expression in dendritic cells turns CD28-Ig from immune adjuvant to suppressant. J Immunol 2005;174:6582-6586.
80. Stockinger B, Hirota K, Duarte J, Veldhoen M. External influences on the immune system via activation of the aryl hydrocarbon receptor. Semin Immunol 2011;23:99-105.
81. Vogel CF, Goth SR, Dong B, Pessah IN, Matsumura F. Aryl hydrocarbon receptor signaling mediates expression of indoleamine 2, 3-dioxygenase. Biochem Biophys Res Commun 2008;375:331-335.
82. Mezrich JD, Fechner JH, Zhang X, Johnson BP, Burlingham WJ, Bradfield CA. An interaction between kynurenine and the aryl hydrocarbon receptor can generate regulatory T cells. J Immunol 2010;185:3190-3198.
83. Nguyen NT, et al. Aryl hydrocarbon receptor negatively regulates dendritic cell immunogenicity via a kynurenine-dependent mechanism. Proc Natl Acad Sci U S A 2010;107:19961-19966.
84. Munn DH, Shafizadeh E, Attwood JT, Bondarev I, Pashine A, Mellor AL. Inhibition of T cell proliferation by macrophage tryptophan catabolism. J Exp Med 1999;189:1363-1372.
85. Munn DH, et al. Prevention of allogeneic fetal rejection by tryptophan catabolism. Science 1998;281:1191-1193.
86. Baban B, Chandler P, McCool D, Marshall B, Munn DH, Mellor AL. Indoleamine 2, 3-dioxygenase expression is restricted to fetal trophoblast giant cells during murine gestation and is maternal genome specific. J Reprod Immunol 2004;61:67-77.
87. Baban B, et al. Physiologic control of IDO competence in splenic dendritic cells. J Immunol 2011;187:2329-2335.
88. O'Connor JC, et al. Induction of IDO by bacille Calmette-Guerin is responsible for development of murine depressive-like behavior. J Immunol 2009;182:3202-3212.
89. Divanovic S, et al. Opposing biological functions of tryptophan catabolizing enzymes during intracellular infection. J Infect Dis 2012;205:152-161.
90. Daubener W, et al. Restriction of Toxoplasma gondii growth in human brain microvascular endothelial cells by activation of indoleamine 2, 3-dioxygenase. Infect Immun 2001;69:6527-6531.
91. Heseler K, Spekker K, Schmidt SK, MacKenzie CR, Daubener W. Antimicrobial and immunoregulatory effects mediated by human lung cells: role of IFN-gamma-induced tryptophan degradation. FEMS Immunol Med Microbiol 2008;52:273-281.
92. Adams O, Besken K, Oberdorfer C, MacKenzie CR, Russing D, Daubener W. Inhibition of human herpes simplex virus type 2 by interferon gamma and tumor necrosis factor alpha is mediated by indoleamine 2, 3-dioxygenase. Microbes Infect 2004;6:806-812.
93. Terajima M, Leporati AM. Role of indoleamine 2, 3-dioxygenase in antiviral activity of interferon-gamma against vaccinia virus. Viral Immunol 2005;18:722-729.
94. Byrne GI, Lehmann LK, Landry GJ. Induction of tryptophan catabolism is the mechanism for gamma-interferon-mediated inhibition of intracellular Chlamydia psittaci replication in T24 cells. Infect Immun 1986;53:347-351.
95. Yeung AW, Wu W, Freewan M, Stocker R, King NJ, Thomas SR. Flavivirus infection induces indoleamine 2, 3-dioxygenase in human monocyte-derived macrophages via tumor necrosis factor and NF-kappaB. J Leukoc Biol 2012;91:657-666.
96. Knubel CP, et al. Indoleamine 2, 3-dioxigenase (IDO) is critical for host resistance against Trypanosoma cruzi. FASEB J 2010;24:2689-2701.
97. Narui K, et al. Anti-infectious activity of tryptophan metabolites in the L-tryptophan-L-kynurenine pathway. Biol Pharm Bull 2009;32:41-44.
98. Makala LH, et al. Leishmania major attenuates host immunity by stimulating local indoleamine 2, 3-dioxygenase expression. J Infect Dis 2011;203:715-725.
99. Boasso A, et al. HIV inhibits CD4+ T-cell proliferation by inducing indoleamine 2, 3-dioxygenase in plasmacytoid dendritic cells. Blood 2007;109:3351-3359.
100. Malleret B, et al. Primary infection with simian immunodeficiency virus: plasmacytoid dendritic cell homing to lymph nodes, type I interferon, and immune suppression. Blood 2008;112:4598-4608.
101. Boasso A, et al. Overactivation of plasmacytoid dendritic cells inhibits antiviral T-cell responses: a model for HIV immunopathogenesis. Blood 2011;118:5152-5162.
102. Potula R, et al. Inhibition of indoleamine 2, 3-dioxygenase (IDO) enhances elimination of virus-infected macrophages in an animal model of HIV-1 encephalitis. Blood 2005;106:2382-2390.
103. Boasso A, et al. Combined effect of antiretroviral therapy and blockade of IDO in SIV-infected rhesus macaques. J Immunol 2009;182:4313-4320.
104. Desvignes L, Ernst JD. Interferon-gamma-responsive nonhematopoietic cells regulate the immune response to Mycobacterium tuberculosis. Immunity 2009;31:974-985.
105. Rani R, Jordan MB, Divanovic S, Herbert DR. IFN-γ-driven IDO production from macrophages protects IL-4Rα-deficient mice against lethality during Schistosoma mansoni infection. Am J Pathol 2012;180:2001-2008.
106. Bozza S, et al. A crucial role for tryptophan catabolism at the host/Candida albicans interface. J Immunol 2005;174:2910-2918.
107. Cheng SC, et al. Candida albicans dampens host defense by downregulating IL-17 production. J Immunol 2010;185:2450-2457.
108. Romani L, et al. Defective tryptophan catabolism underlies inflammation in mouse chronic granulomatous disease. Nature 2008;451:211-215.
109. Van der Sluijs KF, et al. Influenza-induced expression of indoleamine 2, 3-dioxygenase enhances interleukin-10 production and bacterial outgrowth during secondary pneumococcal pneumonia. J Infect Dis 2006;193:214-222.
110. Xin L, et al. Systemic treatment with CpG-B after sublethal rickettsial infection induces mouse death through indoleamine 2, 3-dioxygenase (IDO). PLoS ONE 2012;7:e34062.
111. Hoshi M, et al. The absence of IDO upregulates type I IFN production, resulting in suppression of viral replication in the retrovirus-infected mouse. J Immunol 2010;185:3305-3312.
112. Hoshi M, et al. L-Tryptophan-kynurenine pathway metabolites regulate type I IFNs of acute viral myocarditis in mice. J Immunol 2012;188:3980-3987.
113. Moreau M, et al. Inoculation of Bacillus Calmette-Guerin to mice induces an acute episode of sickness behavior followed by chronic depressive-like behavior. Brain Behav Immun 2008;22:1087-1095.
114. O'Connor JC, et al. Interferon-gamma and tumor necrosis factor-alpha mediate the upregulation of indoleamine 2, 3-dioxygenase and the induction of depressive-like behavior in mice in response to bacillus Calmette-Guerin. J Neurosci 2009;29:4200-4209.
115. Uyttenhove C, et al. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2, 3-dioxygenase. Nat Med 2003;9:1269-1274.
116. Chamuleau ME, et al. High INDO (indoleamine 2, 3-dioxygenase) mRNA level in blasts of acute myeloid leukemic patients predicts poor clinical outcome. Haematologica 2008;93:1894-1898.
117. Brandacher G, et al. Prognostic value of indoleamine 2, 3-dioxygenase expression in colorectal cancer: effect on tumor-infiltrating T cells. Clin Cancer Res 2006;12:1144-1151.
118. Inaba T, et al. Role of the immunosuppressive enzyme indoleamine 2, 3-dioxygenase in the progression of ovarian carcinoma. Gynecol Oncol 2009;115:185-192.
119. Astigiano S, et al. Eosinophil granulocytes account for indoleamine 2, 3-dioxygenase-mediated immune escape in human non-small cell lung cancer. Neoplasia 2005;7:390-396.
120. Suzuki Y, et al. Increased serum kynurenine/tryptophan ratio correlates with disease progression in lung cancer. Lung Cancer 2010;67:361-365.
121. Feder-Mengus C, et al. High expression of indoleamine 2, 3-dioxygenase gene in prostate cancer. Eur J Cancer 2008;44:2266-2275.
122. Okamoto A, et al. Indoleamine 2, 3-dioxygenase serves as a marker of poor prognosis in gene expression profiles of serous ovarian cancer cells. Clin Cancer Res 2005;11:6030-6039.
123. Takao M, et al. Increased synthesis of indoleamine-2, 3-dioxygenase protein is positively associated with impaired survival in patients with serous-type, but not with other types of, ovarian cancer. Oncol Rep 2007;17:1333-1339.
124. Ino K, et al. Indoleamine 2, 3-dioxygenase is a novel prognostic indicator for endometrial cancer. Br J Cancer 2006;95:1555-1561.
125. Sakurai K, et al. [Study of indoleamine 2, 3-dioxygenase expression in patients of esophageal squamous cell carcinoma]. Gan To Kagaku Ryoho 2004;31:1780-1782.
126. Riesenberg R, et al. Expression of indoleamine 2, 3-dioxygenase in tumor endothelial cells correlates with long-term survival of patients with renal cell carcinoma. Clin Cancer Res 2007;13:6993-7002.
127. Ishio T, Goto S, Tahara K, Tone S, Kawano K, Kitano S. Immunoactivative role of indoleamine 2, 3-dioxygenase in human hepatocellular carcinoma. J Gastroenterol Hepatol 2004;19:319-326.
128. Pan K, et al. Expression and prognosis role of indoleamine 2, 3-dioxygenase in hepatocellular carcinoma. J Cancer Res Clin Oncol 2008;134:1247-1253.
129. Munn DH, et al. Potential regulatory function of human dendritic cells expressing indoleamine 2, 3-dioxygenase. Science 2002;297:1867-1870.
130. Lee JR, et al. Pattern of recruitment of immunoregulatory antigen-presenting cells in malignant melanoma. Lab Invest 2003;83:1457-1466.
131. Mansfield AS, Heikkila PS, Vaara AT, vonSmitten KA, Vakkila JM, Leidenius MH. Simultaneous Foxp3 and IDO expression is associated with sentinel lymph node metastases in breast cancer. BMC Cancer 2009;9:231.
132. Witkiewicz A, et al. Expression of indoleamine 2, 3-dioxygenase in metastatic pancreatic ductal adenocarcinoma recruits regulatory T cells to avoid immune detection. J Am Coll Surg 2008;206:849-854, discussion 854-846.
133. Mellor AL, et al. Prevention of T cell-driven complement activation and inflammation by tryptophan catabolism during pregnancy. Nat Immunol 2001;2:64-68.
134. Johnson BA 3rd, Baban B, Mellor AL. Targeting the immunoregulatory indoleamine 2, 3 dioxygenase pathway in immunotherapy. Immunotherapy 2009;1:645-661.
135. Sakurai K, Zou JP, Tschetter JR, Ward JM, Shearer GM. Effect of indoleamine 2, 3-dioxygenase on induction of experimental autoimmune encephalomyelitis. J Neuroimmunol 2002;129:186-196.
136. Xiao BG, Liu X, Link H. Antigen-specific T cell functions are suppressed over the estrogen-dendritic cell-indoleamine 2, 3-dioxygenase axis. Steroids 2004;69:653-659.
137. Matysiak M, Orlowski W, Fortak-Michalska M, Jurewicz A, Selmaj K. Immunoregulatory function of bone marrow mesenchymal stem cells in EAE depends on their differentiation state and secretion of PGE2. J Neuroimmunol 2011;233:106-111.
138. Schroecksnadel K, Winkler C, Duftner C, Wirleitner B, Schirmer M, Fuchs D. Tryptophan degradation increases with stage in patients with rheumatoid arthritis. Clin Rheumatol 2006;25:334-337.
139. Schroecksnadel K, et al. Increased degradation of tryptophan in blood of patients with rheumatoid arthritis. J Rheumatol 2003;30:1935-1939.
140. Liu Y, et al. Therapeutic potential of human umbilical cord mesenchymal stem cells in the treatment of rheumatoid arthritis. Arthritis Res Ther 2010;12:R210.
141. Pigott E, Mandik-Nayak L. Addition of an indoleamine-2, 3, -dioxygenase inhibitor to B cell depletion therapy blocks autoreactive B cell activation and recurrence of arthritis. Arthritis Rheum 2012; doi: 10.1002/art.34406.
142. Xu H, et al. Indoleamine 2, 3-dioxygenase in lung dendritic cells promotes Th2 responses and allergic inflammation. Proc Natl Acad Sci U S A 2008;105:6690-6695.
143. Grohmann U, et al. Reverse signaling through GITR ligand enables dexamethasone to activate IDO in allergy. Nat Med 2007;13:579-586.
144. Cobbold SP, Adams E, Nolan KF, Regateiro FS, Waldmann H. Connecting the mechanisms of T-cell regulation: dendritic cells as the missing link. Immunol Rev 2010;236:203-218.
145. Cobbold SP, et al. Infectious tolerance via the consumption of essential amino acids and mTOR signaling. Proc Natl Acad Sci U S A 2009;106:12055-12060.
146. Rodriguez-Hernandez CJ, et al. The immunosuppressant FK506 uncovers a positive regulatory cross-talk between the Hog1p and Gcn2p pathways. J Biol Chem 2003;278:33887-33895.
147. Reddy P, et al. Histone deacetylase inhibition modulates indoleamine 2, 3-dioxygenase-dependent DC functions and regulates experimental graft-versus-host disease in mice. J Clin Invest 2008;118:2562-2573.
148. Sucher R, et al. IDO and regulatory T cell support are critical for cytotoxic T lymphocyte-associated Ag-4 Ig-mediated long-term solid organ allograft survival. J Immunol 2012;188:37-46.
149. Sun X, et al. IDO-competent-DCs induced by IFN-γ attenuate acute rejection in rat liver transplantation. J Clin Immunol 2012; DOI: 10.1007/s10875-012-9681-4.
150. Jasperson LK, Bucher C, Panoskaltsis-Mortari A, Mellor AL, Munn DH, Blazar BR. Inducing the tryptophan catabolic pathway, indoleamine 2, 3-dioxygenase (IDO), for suppression of graft-versus-host disease (GVHD) lethality. Blood 2009;114:5062-5070.
151. Hou DY, et al. Inhibition of indoleamine 2, 3-dioxygenase in dendritic cells by stereoisomers of 1-methyl-tryptophan correlates with antitumor responses. Cancer Res 2007;67:792-801.
152. Lob S, et al. IDO1 and IDO2 are expressed in human tumors: levo- but not dextro-1-methyl tryptophan inhibits tryptophan catabolism. Cancer Immunol Immunother 2009;58:153-157.
153. Chen W, Liang X, Peterson AJ, Munn DH, Blazar BR. The indoleamine 2, 3-dioxygenase pathway is essential for human plasmacytoid dendritic cell-induced adaptive T regulatory cell generation. J Immunol 2008;181:5396-5404.
154. Banerjee T, et al. A key in vivo antitumor mechanism of action of natural product-based brassinins is inhibition of indoleamine 2, 3-dioxygenase. Oncogene 2008;27:2851-2857.
155. Kumar S, et al. Indoleamine 2, 3-dioxygenase is the anticancer target for a novel series of potent naphthoquinone-based inhibitors. J Med Chem 2008;51:1706-1718.
156. Muller AJ, DuHadaway JB, Donover PS, Sutanto-Ward E, Prendergast GC. Inhibition of indoleamine 2, 3-dioxygenase, an immunoregulatory target of the cancer suppression gene Bin1, potentiates cancer chemotherapy. Nat Med 2005;11:312-319.
157. Mautino MR JF, Collier S, Marcinowicz-Flick A, Kesharwani T. Patent for IDO inhibitors. PCT/US2008/085167.
158. Mautino MR KS, et al.Patent for IDO inhibitors. PCT/US2009/041609.
159. Mautino MR KS, Jaipuri F, Waldo J, Kesharwani T, Zhang X. Patent for IDO inhibitors. PCT/US2010/054289.
160. Mautino MR KS, et al.Patent for IDO inhibitors. PCT/US2012/033245.
161. Yue EW, et al. Discovery of potent competitive inhibitors of indoleamine 2, 3-dioxygenase with in vivo pharmacodynamic activity and efficacy in a mouse melanoma model. J Med Chem 2009;52:7364-7367.
162. Kudo Y, Boyd CA. Characterisation of L-tryptophan transporters in human placenta: a comparison of brush border and basal membrane vesicles. J Physiol 2001;531:405-416.
163. Lob S, Konigsrainer A, Schafer R, Rammensee HG, Opelz G, Terness P. Levo- but not dextro-1-methyl tryptophan abrogates the IDO activity of human dendritic cells. Blood 2008;111:2152-2154.
164. Yuwiler A. Conversion of D- and L-tryptophan to brain serotonin and 5-hydroxyindoleacetic acid and to blood serotonin. J Neurochem 1973;20:1099-1109.
165. Ohara I, Otsuka SI, Yugari Y, Ariyoshi S. Inversion of D-tryptophan to L-tryptophan and excretory patterns in the rat and chick. J Nutr 1980;110:641-648.
166. Triebwasser KC, Swan PB, Henderson LM, Budny JA. Metabolism of D- and L-tryptophan in dogs. J Nutr 1976;106:642-652.
167. Huang TT, et al. Skin delivery of short hairpin RNA of indoleamine 2, 3 dioxygenase induces antitumor immunity against orthotopic and metastatic liver cancer. Cancer Sci 2011;102:2214-2220.
168. Sioud M. Modulation of dendritic cell maturation and function by siRNA-bearing 5′-triphosphate. Methods Mol Biol 2010;629:395-404.
169. Swanson KA, Zheng Y, Heidler KM, Mizobuchi T, Wilkes DS. CDllc+ cells modulate pulmonary immune responses by production of indoleamine 2, 3-dioxygenase. Am J Respir Cell Mol Biol 2004;30:311-318.
170. Liu H, Liu L, Fletcher BS, Visner GA. Novel action of indoleamine 2, 3-dioxygenase attenuating acute lung allograft injury. Am J Respir Crit Care Med 2006;173:566-572.
171. Liu H, Liu L, Liu K, Bizargity P, Hancock WW, Visner GA. Reduced cytotoxic function of effector CD8+ T cells is responsible for indoleamine 2, 3-dioxygenase-dependent immune suppression. J Immunol 2009;183:1022-1031.
172. Leslie M. Immunology. Regulatory T cells get their chance to shine. Science 2011;332:1020-1021.
173. Phillips B, Trucco M, Giannoukakis N. Current state of type 1 diabetes immunotherapy: incremental advances, huge leaps, or more of the same? Clin Dev Immunol 2011;2011:432016.
174. Li L, Huang L, Lemos H, Mautino M, Mellor AL. Altered tryptophan metabolism as a paradigm for good and bad aspects of immune privilege in chronic inflammatory diseases. Front Immun 2012;3:109.
175. Munn DH, Sharma MD, Mellor AL. Ligation of B7-1/B7-2 by human CD4+ T cells triggers indoleamine 2, 3-dioxygenase activity in dendritic cells. J Immunol 2004;172:4100-4110.
176. Fallarino F, et al. CTLA-4-Ig activates forkhead transcription factors and protects dendritic cells from oxidative stress in nonobese diabetic mice. J Exp Med 2004;200:1051-1062.
177. Mellor AL, et al. Cutting edge: induced indoleamine 2, 3 dioxygenase expression in dendritic cell subsets suppresses T cell clonal expansion. J Immunol 2003;171:1652-1655.
178. Kotzor N, Lechmann M, Zinser E, Steinkasserer A. The soluble form of CD83 dramatically changes the cytoskeleton of dendritic cells. Immunobiology 2004;209:129-140.
179. Lan Z, et al. Induction of kidney allograft tolerance by soluble CD83 associated with prevalence of tolerogenic dendritic cells and indoleamine 2, 3-dioxygenase. Transplantation 2010;90:1286-1293.
180. Misaki K, et al. Histone deacetylase inhibition alters dendritic cells to assume a tolerogenic phenotype and ameliorates arthritis in SKG mice. Arthritis Res Ther 2011;13:R77.
181. Choi S, Reddy P. HDAC inhibition and graft versus host disease. Mol Med 2011;17:404-416.
182. Huang L, et al. Engineering nanoparticles as immunomodulatory reagents that activate regulatory T cells. J Immunol 2012;188:4913-4920.
183. Sundrud MS, et al. Halofuginone inhibits TH17 cell differentiation by activating the amino acid starvation response. Science 2009;324:1334-1338.
184. Keller TL, et al. Halofuginone and other febrifugine derivatives inhibit prolyl-tRNA synthetase. Nat Chem Biol 2012;8:311-317.
185. Yan Y, et al. IDO upregulates regulatory T cells via tryptophan catabolite and suppresses encephalitogenic T cell responses in experimental autoimmune encephalomyelitis. J Immunol 2010;185:5953-5961.
186. Criado G, Simelyte E, Inglis JJ, Essex D, Williams RO. Indoleamine 2, 3 dioxygenase-mediated tryptophan catabolism regulates accumulation of Th1/Th17 cells in the joint in collagen-induced arthritis. Arthritis Rheum 2009;60:1342-1351.
187. Jaen O, Rulle S, Bessis N, Zago A, Boissier MC, Falgarone G. Dendritic cells modulated by innate immunity improve collagen-induced arthritis and induce regulatory T cells in vivo. Immunology 2009;126:35-44.
188. Taher YA, et al. Indoleamine 2, 3-dioxygenase-dependent tryptophan metabolites contribute to tolerance induction during allergen immunotherapy in a mouse model. J Allergy Clin Immunol 2008;121:983-991.
189. Gordon JR, Li F, Nayyar A, Xiang J, Zhang X. CD8 alpha+, but not CD8 alpha-, dendritic cells tolerize Th2 responses via contact-dependent and -independent mechanisms, and reverse airway hyperresponsiveness, Th2, and eosinophil responses in a mouse model of asthma. J Immunol 2005;175:1516-1522.