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Epigenetic Changes in Inflammatory and Autoimmune Diseases

  • Helene Myrtue Nielsen
  • Jörg Tost
Part of the Subcellular Biochemistry book series (SCBI, volume 61)

Abstract

In higher eukaryotic organisms epigenetic modifications are crucial for proper chromatin folding and thereby proper regulation of gene expression. In the last years the involvement of aberrant epigenetic modifications in inflammatory and autoimmune diseases has been recognized and attracted significant interest. However, the epigenetic mechanisms underlying the different disease phenotypes are still poorly understood. As autoimmune and inflammatory diseases are at least partly T cell mediated, we will provide in this chapter an introduction to the epigenetics of T cell differentiation followed by a summary of the current knowledge on aberrant epigenetic modifications that dysfunctional T cells display in various diseases such as type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, inflammatory bowel disease, and asthma.

Keywords

Systemic Lupus Erythematosus Patient Treg Cell HDAC Inhibitor Diesel Exhaust Particle Inflammatory Bowel Disease Pathogenesis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Afkarian M, Sedy JR, Yang J, Jacobson NG, Cereb N, Yang SY, Murphy TL, Murphy KM (2002) T-bet is a STAT1-induced regulator of IL-12R expression in naive CD4+ T cells. Nat Immunol 3:549–557PubMedCrossRefGoogle Scholar
  2. Aho K, Koskenvuo M, Tuominen J, Kaprio J (1986) Occurrence of rheumatoid arthritis in a nationwide series of twins. J Rheumatol 13:899–902PubMedGoogle Scholar
  3. Ansel KM, Lee DU, Rao A (2003) An epigenetic view of helper T cell differentiation. Nat Immunol 4:616–623PubMedCrossRefGoogle Scholar
  4. Ansel KM, Djuretic I, Tanasa B, Rao A (2006) Regulation of Th2 differentiation and Il4 locus accessibility. Annu Rev Immunol 24:607–656PubMedCrossRefGoogle Scholar
  5. Arif M, Pradhan SK, Thanuja GR, Vedamurthy BM, Agrawal S, Dasgupta D, Kundu TK (2009) Mechanism of p300 specific histone acetyltransferase inhibition by small molecules. J Med Chem 52:267–277PubMedCrossRefGoogle Scholar
  6. Ashkenazi A, Dixit VM (1998) Death receptors: signaling and modulation. Science 281:1305–1308PubMedCrossRefGoogle Scholar
  7. Aune TM, Collins PL, Chang S (2009) Epigenetics and T helper 1 differentiation. Immunology 126:299–305PubMedCrossRefGoogle Scholar
  8. Avni O, Lee D, Macian F, Szabo SJ, Glimcher LH, Rao A (2002) T(H) cell differentiation is accompanied by dynamic changes in histone acetylation of cytokine genes. Nat Immunol 3:643–651PubMedCrossRefGoogle Scholar
  9. Baccarelli A, Wright RO, Bollati V, Tarantini L, Litonjua AA, Suh HH, Zanobetti A, Sparrow D, Vokonas PS, Schwartz J (2009) Rapid DNA methylation changes after exposure to traffic particles. Am J Respir Crit Care Med 179:572–578PubMedCrossRefGoogle Scholar
  10. Baguet A, Bix M (2004) Chromatin landscape dynamics of the Il4-Il13 locus during T helper 1 and 2 development. Proc Natl Acad Sci U S A 101:11410–11415PubMedCrossRefGoogle Scholar
  11. Balasubramani A, Shibata Y, Crawford GE, Baldwin AS, Hatton RD, Weaver CT (2010) Modular utilization of distal cis-regulatory elements controls Ifng gene expression in T cells activated by distinct stimuli. Immunity 33:35–47PubMedCrossRefGoogle Scholar
  12. Ballestar E (2010) Epigenetics lessons from twins: prospects for autoimmune disease. Clin Rev Allergy Immunol 39:30–41PubMedCrossRefGoogle Scholar
  13. Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z, Wei G, Chepelev I, Zhao K (2007) High-resolution profiling of histone methylations in the human genome. Cell 129:823–837PubMedCrossRefGoogle Scholar
  14. Bovenschen HJ, van de Kerkhof PC, van Erp PE, Woestenenk R, Joosten I, Koenen HJ (2011) Foxp3+ regulatory T cells of psoriasis patients easily differentiate into IL-17A-producing cells and are found in lesional skin. J Invest Dermatol 131:1853–1860PubMedCrossRefGoogle Scholar
  15. Boyle AP, Davis S, Shulha HP, Meltzer P, Margulies EH, Weng Z, Furey TS, Crawford GE (2008) High-resolution mapping and characterization of open chromatin across the genome. Cell 132:311–322PubMedCrossRefGoogle Scholar
  16. Brand S, Teich R, Dicke T, Harb H, Yildirim AO, Tost J, Schneider-Stock R, Waterland RA, Bauer U-M, von Mutius E, Garn H, Pfefferle PI, Renz H (2011) Epigenetic regulation in murine offspring as a novel mechanism for transmaternal asthma protection induced by microbes. J Allergy Clin Immunol 128:618–625PubMedCrossRefGoogle Scholar
  17. Bream JH, Hodge DL, Gonsky R, Spolski R, Leonard WJ, Krebs S, Targan S, Morinobu A, O’Shea JJ, Young HA (2004) A distal region in the interferon-gamma gene is a site of epigenetic remodeling and transcriptional regulation by interleukin-2. J Biol Chem 279:41249–41257PubMedCrossRefGoogle Scholar
  18. Brooks WH (2010) X chromosome inactivation and autoimmunity. Clin Rev Allergy Immunol 39:20–29PubMedCrossRefGoogle Scholar
  19. Buckner JH (2010) Mechanisms of impaired regulation by CD4(+)CD25(+)FOXP3(+) regulatory T cells in human autoimmune diseases. Nat Rev Immunol 10:849–859PubMedCrossRefGoogle Scholar
  20. Calvanese V, Lara E, Kahn A, Fraga MF (2009) The role of epigenetics in aging and age-related diseases. Ageing Res Rev 8:268–276PubMedCrossRefGoogle Scholar
  21. Chang S, Aune TM (2007) Dynamic changes in histone-methylation ‘marks’ across the locus encoding interferon-gamma during the differentiation of T helper type 2 cells. Nat Immunol 8:723–731PubMedCrossRefGoogle Scholar
  22. Corvetta A, Della Bitta R, Luchetti MM, Pomponio G (1991) 5-Methylcytosine content of DNA in blood, synovial mononuclear cells and synovial tissue from patients affected by autoimmune rheumatic diseases. J Chromatogr 566:481–491PubMedCrossRefGoogle Scholar
  23. Cosio BG, Mann B, Ito K, Jazrawi E, Barnes PJ, Chung KF, Adcock IM (2004) Histone acetylase and deacetylase activity in alveolar macrophages and blood mononocytes in asthma. Am J Respir Crit Care Med 170:141–147PubMedCrossRefGoogle Scholar
  24. Djuretic IM, Levanon D, Negreanu V, Groner Y, Rao A, Ansel KM (2007) Transcription factors T-bet and Runx3 cooperate to activate Ifng and silence Il4 in T helper type 1 cells. Nat Immunol 8:145–153PubMedCrossRefGoogle Scholar
  25. Durrant DM, Metzger DW (2010) Emerging roles of T helper subsets in the pathogenesis of asthma. Immunol Invest 39:526–549PubMedCrossRefGoogle Scholar
  26. Eizirik DL, Colli ML, Ortis F (2009) The role of inflammation in insulitis and beta-cell loss in type 1 diabetes. Nat Rev Endocrinol 5:219–226PubMedCrossRefGoogle Scholar
  27. Fields PE, Kim ST, Flavell RA (2002) Cutting edge: changes in histone acetylation at the IL-4 and IFN-gamma loci accompany Th1/Th2 differentiation. J Immunol 169:647–650PubMedGoogle Scholar
  28. Firestein GS (2003) Evolving concepts of rheumatoid arthritis. Nature 423:356–361PubMedCrossRefGoogle Scholar
  29. Fraga MF (2009) Genetic and epigenetic regulation of aging. Curr Opin Immunol 21:446–453PubMedCrossRefGoogle Scholar
  30. Fraga MF, Ballestar E, Paz MF, Ropero S, Setien F, Ballestar ML, Heine-Suner D, Cigudosa JC, Urioste M, Benitez J, Boix-Chornet M, Sanchez-Aguilera A, Ling C, Carlsson E, Poulsen P, Vaag A, Stephan Z, Spector TD, Wu YZ, Plass C, Esteller M (2005) Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci U S A 102:10604–10609PubMedCrossRefGoogle Scholar
  31. Glauben R, Batra A, Fedke I, Zeitz M, Lehr HA, Leoni F, Mascagni P, Fantuzzi G, Dinarello CA, Siegmund B (2006) Histone hyperacetylation is associated with amelioration of experimental colitis in mice. J Immunol 176:5015–5022PubMedGoogle Scholar
  32. Grogan JL, Mohrs M, Harmon B, Lacy DA, Sedat JW, Locksley RM (2001) Early transcription and silencing of cytokine genes underlie polarization of T helper cell subsets. Immunity 14:205–215PubMedCrossRefGoogle Scholar
  33. Hamalainen-Laanaya HK, Kobie JJ, Chang C, Zeng WP (2007) Temporal and spatial changes of histone 3 K4 dimethylation at the IFN-gamma gene during Th1 and Th2 cell differentiation. J Immunol 179:6410–6415PubMedGoogle Scholar
  34. Hatton RD, Harrington LE, Luther RJ, Wakefield T, Janowski KM, Oliver JR, Lallone RL, Murphy KM, Weaver CT (2006) A distal conserved sequence element controls Ifng gene expression by T cells and NK cells. Immunity 25:717–729PubMedCrossRefGoogle Scholar
  35. Hew M, Bhavsar P, Torrego A, Meah S, Khorasani N, Barnes PJ, Adcock I, Chung KF (2006) Relative corticosteroid insensitivity of peripheral blood mononuclear cells in severe asthma. Am J Respir Crit Care Med 174:134–141PubMedCrossRefGoogle Scholar
  36. Holliday R (2006) Epigenetics: a historical overview. Epigenetics 1:76–80PubMedCrossRefGoogle Scholar
  37. Huber LC, Brock M, Hemmatazad H, Giger OT, Moritz F, Trenkmann M, Distler JH, Gay RE, Kolling C, Moch H, Michel BA, Gay S, Distler O, Jungel A (2007) Histone deacetylase/acetylase activity in total synovial tissue derived from rheumatoid arthritis and osteoarthritis patients. Arthritis Rheum 56:1087–1093PubMedCrossRefGoogle Scholar
  38. Hutchins AS, Mullen AC, Lee HW, Sykes KJ, High FA, Hendrich BD, Bird AP, Reiner SL (2002) Gene silencing quantitatively controls the function of a developmental trans-activator. Mol Cell 10:81–91PubMedCrossRefGoogle Scholar
  39. Ivanov II, Zhou L, Littman DR (2007) Transcriptional regulation of Th17 cell differentiation. Semin Immunol 19:409–417PubMedCrossRefGoogle Scholar
  40. Javierre BM, Fernandez AF, Richter J, Al-Shahrour F, Martin-Subero JI, Rodriguez-Ubreva J, Berdasco M, Fraga MF, O’Hanlon TP, Rider LG, Jacinto FV, Lopez-Longo FJ, Dopazo J, Forn M, Peinado MA, Carreno L, Sawalha AH, Harley JB, Siebert R, Esteller M, Miller FW, Ballestar E (2010) Changes in the pattern of DNA methylation associate with twin discordance in systemic lupus erythematosus. Genome Res 20:170–179PubMedCrossRefGoogle Scholar
  41. Karouzakis E, Gay RE, Michel BA, Gay S, Neidhart M (2009) DNA hypomethylation in rheumatoid arthritis synovial fibroblasts. Arthritis Rheum 60:3613–3622PubMedCrossRefGoogle Scholar
  42. Kimura A, Kishimoto T (2010) IL-6: regulator of Treg/Th17 balance. Eur J Immunol 40:1830–1835PubMedCrossRefGoogle Scholar
  43. Koenen HJ, Smeets RL, Vink PM, van Rijssen E, Boots AM, Joosten I (2008) Human CD25highFoxp3pos regulatory T cells differentiate into IL-17-producing cells. Blood 112:2340–2352PubMedCrossRefGoogle Scholar
  44. Kouzarides T (2007) Chromatin modifications and their function. Cell 128:693–705PubMedCrossRefGoogle Scholar
  45. Koyanagi M, Baguet A, Martens J, Margueron R, Jenuwein T, Bix M (2005) EZH2 and histone 3 trimethyl lysine 27 associated with Il4 and Il13 gene silencing in Th1 cells. J Biol Chem 280:31470–31477PubMedCrossRefGoogle Scholar
  46. Kristensen LS, Nielsen HM, Hansen LL (2009) Epigenetics and cancer treatment. Eur J Pharmacol 625:131–142PubMedCrossRefGoogle Scholar
  47. Krueger GG, Duvic M (1994) Epidemiology of psoriasis: clinical issues. J Invest Dermatol 102:14S–18SPubMedCrossRefGoogle Scholar
  48. Kryczek I, Wu K, Zhao E, Wei S, Vatan L, Szeliga W, Huang E, Greenson J, Chang A, Rolinski J, Radwan P, Fang J, Wang G, Zou W (2011) IL-17+ regulatory T cells in the microenvironments of chronic inflammation and cancer. J Immunol 186:4388–4395PubMedCrossRefGoogle Scholar
  49. Larche M (2007) Regulatory T cells in allergy and asthma. Chest 132:1007–1014PubMedCrossRefGoogle Scholar
  50. Lau OD, Kundu TK, Soccio RE, Ait-Si-Ali S, Khalil EM, Vassilev A, Wolffe AP, Nakatani Y, Roeder RG, Cole PA (2000) HATs off: selective synthetic inhibitors of the histone acetyltransferases p300 and PCAF. Mol Cell 5:589–595PubMedCrossRefGoogle Scholar
  51. Le Gros G, Ben-Sasson SZ, Seder R, Finkelman FD, Paul WE (1990) Generation of interleukin 4 (IL-4)-producing cells in vivo and in vitro: IL-2 and IL-4 are required for in vitro generation of IL-4-producing cells. J Exp Med 172:921–929PubMedCrossRefGoogle Scholar
  52. Lee DU, Agarwal S, Rao A (2002) Th2 lineage commitment and efficient IL-4 production involves extended demethylation of the IL-4 gene. Immunity 16:649–660PubMedCrossRefGoogle Scholar
  53. Lee DU, Avni O, Chen L, Rao A (2004) A distal enhancer in the interferon-gamma (IFN-gamma) locus revealed by genome sequence comparison. J Biol Chem 279:4802–4810PubMedCrossRefGoogle Scholar
  54. Letimier FA, Passini N, Gasparian S, Bianchi E, Rogge L (2007) Chromatin remodeling by the SWI/SNF-like BAF complex and STAT4 activation synergistically induce IL-12Rbeta2 expression during human Th1 cell differentiation. EMBO J 26:1292–1302PubMedCrossRefGoogle Scholar
  55. Lighvani AA, Frucht DM, Jankovic D, Yamane H, Aliberti J, Hissong BD, Nguyen BV, Gadina M, Sher A, Paul WE, O’Shea JJ (2001) T-bet is rapidly induced by interferon-gamma in lymphoid and myeloid cells. Proc Natl Acad Sci U S A 98:15137–15142PubMedCrossRefGoogle Scholar
  56. Lin HS, Hu CY, Chan HY, Liew YY, Huang HP, Lepescheux L, Bastianelli E, Baron R, Rawadi G, Clement-Lacroix P (2007) Anti-rheumatic activities of histone deacetylase (HDAC) inhibitors in vivo in collagen-induced arthritis in rodents. Br J Pharmacol 150:862–872PubMedCrossRefGoogle Scholar
  57. Liu J, Ballaney M, Al-alem U, Quan C, Jin X, Perera F, Chen LC, Miller RL (2008) Combined inhaled diesel exhaust particles and allergen exposure alter methylation of T helper genes and IgE production in vivo. Toxicol Sci 102:76–81PubMedCrossRefGoogle Scholar
  58. Liu CC, Fang TJ, Ou TT, Wu CC, Li RN, Lin YC, Lin CH, Tsai WC, Liu HW, Yen JH (2011) Global DNA methylation, DNMT1, and MBD2 in patients with rheumatoid arthritis. Immunol Lett 135:96–99PubMedCrossRefGoogle Scholar
  59. Loots GG, Locksley RM, Blankespoor CM, Wang ZE, Miller W, Rubin EM, Frazer KA (2000) Identification of a coordinate regulator of interleukins 4, 13, and 5 by cross-species sequence comparisons. Science 288:136–140PubMedCrossRefGoogle Scholar
  60. Lu Q, Wu A, Tesmer L, Ray D, Yousif N, Richardson B (2007) Demethylation of CD40LG on the inactive X in T cells from women with lupus. J Immunol 179:6352–6358PubMedGoogle Scholar
  61. Lucey DR, Clerici M, Shearer GM (1996) Type 1 and type 2 cytokine dysregulation in human infectious, neoplastic, and inflammatory diseases. Clin Microbiol Rev 9:532–562PubMedGoogle Scholar
  62. Makar KW, Perez-Melgosa M, Shnyreva M, Weaver WM, Fitzpatrick DR, Wilson CB (2003) Active recruitment of DNA methyltransferases regulates interleukin 4 in thymocytes and T cells. Nat Immunol 4:1183–1190PubMedCrossRefGoogle Scholar
  63. Mastronardi FG, Noor A, Wood DD, Paton T, Moscarello MA (2007) Peptidyl argininedeiminase 2 CpG island in multiple sclerosis white matter is hypomethylated. J Neurosci Res 85:2006–2016PubMedCrossRefGoogle Scholar
  64. McGeachy MJ, Cua DJ (2008) Th17 cell differentiation: the long and winding road. Immunity 28:445–453PubMedCrossRefGoogle Scholar
  65. McGee HS, Agrawal DK (2006) TH2 cells in the pathogenesis of airway remodeling: regulatory T cells a plausible panacea for asthma. Immunol Res 35:219–232PubMedCrossRefGoogle Scholar
  66. Meda F, Folci M, Baccarelli A, Selmi C (2011) The epigenetics of autoimmunity. Cell Mol Immunol 8:226–236PubMedCrossRefGoogle Scholar
  67. Miao F, Smith DD, Zhang L, Min A, Feng W, Natarajan R (2008) Lymphocytes from patients with type 1 diabetes display a distinct profile of chromatin histone H3 lysine 9 dimethylation: an epigenetic study in diabetes. Diabetes 57:3189–3198PubMedCrossRefGoogle Scholar
  68. Miller SA, Huang AC, Miazgowicz MM, Brassil MM, Weinmann AS (2008) Coordinated but physically separable interaction with H3K27-demethylase and H3K4-methyltransferase activities are required for T-box protein-mediated activation of developmental gene expression. Genes Dev 22:2980–2993PubMedCrossRefGoogle Scholar
  69. Mishra N, Brown DR, Olorenshaw IM, Kammer GM (2001) Trichostatin A reverses skewed expression of CD154, interleukin-10, and interferon-gamma gene and protein expression in lupus T cells. Proc Natl Acad Sci USA 98:2628–2633PubMedCrossRefGoogle Scholar
  70. Moscarello MA, Wood DD, Ackerley C, Boulias C (1994) Myelin in multiple sclerosis is developmentally immature. J Clin Invest 94:146–154PubMedCrossRefGoogle Scholar
  71. Mottet C, Uhlig HH, Powrie F (2003) Cutting edge: cure of colitis by CD4  +  CD25+ regulatory T cells. J Immunol 170:3939–3943PubMedGoogle Scholar
  72. Murdaca G, Colombo BM, Puppo F (2011) The role of Th17 lymphocytes in the autoimmune and chronic inflammatory diseases. Intern Emerg Med 6:487–495PubMedCrossRefGoogle Scholar
  73. Murphy KM, Reiner SL (2002) The lineage decisions of helper T cells. Nat Rev Immunol 2:933–944PubMedCrossRefGoogle Scholar
  74. Myzak MC, Dashwood RH (2006) Histone deacetylases as targets for dietary cancer preventive agents: lessons learned with butyrate, diallyl disulfide, and sulforaphane. Curr Drug Targets 7:443–452PubMedCrossRefGoogle Scholar
  75. Nadeau K, McDonald-Hyman C, Noth EM, Pratt B, Hammond SK, Balmes J, Tager I (2010) Ambient air pollution impairs regulatory T-cell function in asthma. J Allergy Clin Immunol 126(845–852):e810Google Scholar
  76. Naoe Y, Setoguchi R, Akiyama K, Muroi S, Kuroda M, Hatam F, Littman DR, Taniuchi I (2007) Repression of interleukin-4 in T helper type 1 cells by Runx/Cbf beta binding to the Il4 silencer. J Exp Med 204:1749–1755PubMedCrossRefGoogle Scholar
  77. Nardone J, Lee DU, Ansel KM, Rao A (2004) Bioinformatics for the ‘bench biologist’: how to find regulatory regions in genomic DNA. Nat Immunol 5:768–774PubMedCrossRefGoogle Scholar
  78. Neidhart M, Rethage J, Kuchen S, Kunzler P, Crowl RM, Billingham ME, Gay RE, Gay S (2000) Retrotransposable L1 elements expressed in rheumatoid arthritis synovial tissue: association with genomic DNA hypomethylation and influence on gene expression. Arthritis Rheum 43:2634–2647PubMedCrossRefGoogle Scholar
  79. Nishida K, Komiyama T, Miyazawa S, Shen ZN, Furumatsu T, Doi H, Yoshida A, Yamana J, Yamamura M, Ninomiya Y, Inoue H, Asahara H (2004) Histone deacetylase inhibitor suppression of autoantibody-mediated arthritis in mice via regulation of p16INK4a and p21(WAF1/Cip1) expression. Arthritis Rheum 50:3365–3376PubMedCrossRefGoogle Scholar
  80. Ouyang W, Lohning M, Gao Z, Assenmacher M, Ranganath S, Radbruch A, Murphy KM (2000) Stat6-independent GATA-3 autoactivation directs IL-4-independent Th2 development and commitment. Immunity 12:27–37PubMedCrossRefGoogle Scholar
  81. Ouyang W, Kolls JK, Zheng Y (2008) The biological functions of T helper 17 cell effector cytokines in inflammation. Immunity 28:454–467PubMedCrossRefGoogle Scholar
  82. Pai SY, Truitt ML, Ho IC (2004) GATA-3 deficiency abrogates the development and maintenance of T helper type 2 cells. Proc Natl Acad Sci U S A 101:1993–1998PubMedCrossRefGoogle Scholar
  83. Pan W, Zhu S, Yuan M, Cui H, Wang L, Luo X, Li J, Zhou H, Tang Y, Shen N (2010) MicroRNA-21 and microRNA-148a contribute to DNA hypomethylation in lupus CD4+ T cells by directly and indirectly targeting DNA methyltransferase 1. J Immunol 184:6773–6781PubMedCrossRefGoogle Scholar
  84. Perera F, Tang WY, Herbstman J, Tang D, Levin L, Miller R, Ho SM (2009) Relation of DNA methylation of 5′-CpG island of ACSL3 to transplacental exposure to airborne polycyclic aromatic hydrocarbons and childhood asthma. PLoS One 4:e4488PubMedCrossRefGoogle Scholar
  85. Placek K, Coffre M, Maiella S, Bianchi E, Rogge L (2009) Genetic and epigenetic networks controlling T helper 1 cell differentiation. Immunology 127:155–162PubMedCrossRefGoogle Scholar
  86. Presky DH, Yang H, Minetti LJ, Chua AO, Nabavi N, Wu CY, Gately MK, Gubler U (1996) A functional interleukin 12 receptor complex is composed of two beta-type cytokine receptor subunits. Proc Natl Acad Sci U S A 93:14002–14007PubMedCrossRefGoogle Scholar
  87. Reilly CM, Thomas M, Gogal R Jr, Olgun S, Santo A, Sodhi R, Samy ET, Peng SL, Gilkeson GS, Mishra N (2008) The histone deacetylase inhibitor trichostatin A upregulates regulatory T cells and modulates autoimmunity in NZB/W F1 mice. J Autoimmun 31:123–130PubMedCrossRefGoogle Scholar
  88. Ribeiro de Almeida C, Heath H, Krpic S, Dingjan GM, van Hamburg JP, Bergen I, van de Nobelen S, Sleutels F, Grosveld F, Galjart N, Hendriks RW (2009) Critical role for the transcription regulator CCCTC-binding factor in the control of Th2 cytokine expression. J Immunol 182:999–1010PubMedGoogle Scholar
  89. Richardson B (1986) Effect of an inhibitor of DNA methylation on T cells. II. 5-Azacytidine induces self-reactivity in antigen-specific T4+ cells. Hum Immunol 17:456–470PubMedCrossRefGoogle Scholar
  90. Richardson B, Scheinbart L, Strahler J, Gross L, Hanash S, Johnson M (1990) Evidence for impaired T cell DNA methylation in systemic lupus erythematosus and rheumatoid arthritis. Arthritis Rheum 33:1665–1673PubMedCrossRefGoogle Scholar
  91. Robinson DS, Hamid Q, Ying S, Tsicopoulos A, Barkans J, Bentley AM, Corrigan C, Durham SR, Kay AB (1992) Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma. N Engl J Med 326:298–304PubMedCrossRefGoogle Scholar
  92. Sakaguchi S, Ono M, Setoguchi R, Yagi H, Hori S, Fehervari Z, Shimizu J, Takahashi T, Nomura T (2006) Foxp3+ CD25+ CD4+ natural regulatory T cells in dominant self-tolerance and autoimmune disease. Immunol Rev 212:8–27PubMedCrossRefGoogle Scholar
  93. Sakaguchi S, Yamaguchi T, Nomura T, Ono M (2008) Regulatory T cells and immune tolerance. Cell 133:775–787PubMedCrossRefGoogle Scholar
  94. Sawalha AH, Harley JB (2004) Antinuclear autoantibodies in systemic lupus erythematosus. Curr Opin Rheumatol 16:534–540PubMedCrossRefGoogle Scholar
  95. Schoenborn JR, Dorschner MO, Sekimata M, Santer DM, Shnyreva M, Fitzpatrick DR, Stamatoyannopoulos JA, Wilson CB (2007) Comprehensive epigenetic profiling identifies multiple distal regulatory elements directing transcription of the gene encoding interferon-gamma. Nat Immunol 8:732–742PubMedCrossRefGoogle Scholar
  96. Selmi C (2009) What is hot in autoimmunity. Acta Reumatol Port 34:580–588PubMedGoogle Scholar
  97. Selvi BR, Mohankrishna DV, Ostwal YB, Kundu TK (2010) Small molecule modulators of histone acetylation and methylation: a disease perspective. Biochim Biophys Acta 1799:810–828PubMedCrossRefGoogle Scholar
  98. Sgouroudis E, Piccirillo CA (2009) Control of type 1 diabetes by CD4  +  Foxp3+ regulatory T cells: lessons from mouse models and implications for human disease. Diabetes Metab Res Rev 25:208–218PubMedCrossRefGoogle Scholar
  99. Shnyreva M, Weaver WM, Blanchette M, Taylor SL, Tompa M, Fitzpatrick DR, Wilson CB (2004) Evolutionarily conserved sequence elements that positively regulate IFN-gamma expression in T cells. Proc Natl Acad Sci U S A 101:12622–12627PubMedCrossRefGoogle Scholar
  100. Soto ME, Vallejo M, Guillen F, Simon JA, Arena E, Reyes PA (2004) Gender impact in systemic lupus erythematosus. Clin Exp Rheumatol 22:713–721PubMedGoogle Scholar
  101. Stimson L, Rowlands MG, Newbatt YM, Smith NF, Raynaud FI, Rogers P, Bavetsias V, Gorsuch S, Jarman M, Bannister A, Kouzarides T, McDonald E, Workman P, Aherne GW (2005) Isothiazolones as inhibitors of PCAF and p300 histone acetyltransferase activity. Mol Cancer Ther 4:1521–1532PubMedCrossRefGoogle Scholar
  102. Takami N, Osawa K, Miura Y, Komai K, Taniguchi M, Shiraishi M, Sato K, Iguchi T, Shiozawa K, Hashiramoto A, Shiozawa S (2006) Hypermethylated promoter region of DR3, the death receptor 3 gene, in rheumatoid arthritis synovial cells. Arthritis Rheum 54:779–787PubMedCrossRefGoogle Scholar
  103. Takemoto N, Koyano-Nakagawa N, Yokota T, Arai N, Miyatake S, Arai K (1998) Th2-specific DNase I-hypersensitive sites in the murine IL-13 and IL-4 intergenic region. Int Immunol 10:1981–1985PubMedCrossRefGoogle Scholar
  104. Tao R, de Zoeten EF, Ozkaynak E, Chen C, Wang L, Porrett PM, Li B, Turka LA, Olson EN, Greene MI, Wells AD, Hancock WW (2007) Deacetylase inhibition promotes the generation and function of regulatory T cells. Nat Med 13:1299–1307PubMedCrossRefGoogle Scholar
  105. Taylor A, Verhagen J, Akdis CA, Akdis M (2005) T regulatory cells and allergy. Microbes Infect 7:1049–1055PubMedCrossRefGoogle Scholar
  106. Thieu VT, Yu Q, Chang HC, Yeh N, Nguyen ET, Sehra S, Kaplan MH (2008) Signal transducer and activator of transcription 4 is required for the transcription factor T-bet to promote T helper 1 cell-fate determination. Immunity 29:679–690PubMedCrossRefGoogle Scholar
  107. Tost J (2008) Epigenetics. Caister Academic Press, Norfolk, UKGoogle Scholar
  108. Tsaprouni LG, Ito K, Powell JJ, Adcock IM, Punchard N (2011) Differential patterns of histone acetylation in inflammatory bowel diseases. J Inflamm (Lond) 8:1CrossRefGoogle Scholar
  109. Tykocinski LO, Hajkova P, Chang HD, Stamm T, Sozeri O, Lohning M, Hu-Li J, Niesner U, Kreher S, Friedrich B, Pannetier C, Grutz G, Walter J, Paul WE, Radbruch A (2005) A critical control element for interleukin-4 memory expression in T helper lymphocytes. J Biol Chem 280:28177–28185PubMedCrossRefGoogle Scholar
  110. Usui T, Nishikomori R, Kitani A, Strober W (2003) GATA-3 suppresses Th1 development by downregulation of Stat4 and not through effects on IL-12Rbeta2 chain or T-bet. Immunity 18:415–428PubMedCrossRefGoogle Scholar
  111. Usui T, Preiss JC, Kanno Y, Yao ZJ, Bream JH, O’Shea JJ, Strober W (2006) T-bet regulates Th1 responses through essential effects on GATA-3 function rather than on IFNG gene acetylation and transcription. J Exp Med 203:755–766PubMedCrossRefGoogle Scholar
  112. Vel Szic KS, Ndlovu MN, Haegeman G, Vanden Berghe W (2010) Nature or nurture: let food be your epigenetic medicine in chronic inflammatory disorders. Biochem Pharmacol 80:1816–1832CrossRefGoogle Scholar
  113. Weaver CT, Hatton RD, Mangan PR, Harrington LE (2007) IL-17 family cytokines and the expanding diversity of effector T cell lineages. Annu Rev Immunol 25:821–852PubMedCrossRefGoogle Scholar
  114. Wei G, Wei L, Zhu J, Zang C, Hu-Li J, Yao Z, Cui K, Kanno Y, Roh TY, Watford WT, Schones DE, Peng W, Sun HW, Paul WE, O’Shea JJ, Zhao K (2009) Global mapping of H3K4me3 and H3K27me3 reveals specificity and plasticity in lineage fate determination of differentiating CD4+ T cells. Immunity 30:155–167PubMedCrossRefGoogle Scholar
  115. Whitelaw NC, Whitelaw E (2006) How lifetimes shape epigenotype within and across generations. Hum Mol Genet 15(Spec No 2):R131–137Google Scholar
  116. Wilson CB, Rowell E, Sekimata M (2009) Epigenetic control of T-helper-cell differentiation. Nat Rev Immunol 9:91–105PubMedCrossRefGoogle Scholar
  117. Wulfing C, Sumen C, Sjaastad MD, Wu LC, Dustin ML, Davis MM (2002) Costimulation and endogenous MHC ligands contribute to T cell recognition. Nat Immunol 3:42–47PubMedCrossRefGoogle Scholar
  118. Yamashita M, Ukai-Tadenuma M, Kimura M, Omori M, Inami M, Taniguchi M, Nakayama T (2002) Identification of a conserved GATA3 response element upstream proximal from the interleukin-13 gene locus. J Biol Chem 277:42399–42408PubMedCrossRefGoogle Scholar
  119. Yamashita M, Hirahara K, Shinnakasu R, Hosokawa H, Norikane S, Kimura MY, Hasegawa A, Nakayama T (2006) Crucial role of MLL for the maintenance of memory T helper type 2 cell responses. Immunity 24:611–622PubMedCrossRefGoogle Scholar
  120. Yang Y, Ochando JC, Bromberg JS, Ding Y (2007) Identification of a distant T-bet enhancer responsive to IL-12/Stat4 and IFNgamma/Stat1 signals. Blood 110:2494–2500PubMedCrossRefGoogle Scholar
  121. Yang XO, Pappu BP, Nurieva R, Akimzhanov A, Kang HS, Chung Y, Ma L, Shah B, Panopoulos AD, Schluns KS, Watowich SS, Tian Q, Jetten AM, Dong C (2008) T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma. Immunity 28:29–39PubMedCrossRefGoogle Scholar
  122. Zhao M, Sun Y, Gao F, Wu X, Tang J, Yin H, Luo Y, Richardson B, Lu Q (2010a) Epigenetics and SLE: RFX1 downregulation causes CD11a and CD70 overexpression by altering epigenetic modifications in lupus CD4+ T cells. J Autoimmun 35:58–69PubMedCrossRefGoogle Scholar
  123. Zhao M, Wu X, Zhang Q, Luo S, Liang G, Su Y, Tan Y, Lu Q (2010b) RFX1 regulates CD70 and CD11a expression in lupus T cells by recruiting the histone methyltransferase SUV39H1. Arthritis Res Ther 12:R227PubMedCrossRefGoogle Scholar
  124. Zheng Q, Xu Y, Liu Y, Zhang B, Li X, Guo F, Zhao Y (2009) Induction of Foxp3 demethylation increases regulatory CD4  +  CD25+ T cells and prevents the occurrence of diabetes in mice. J Mol Med 87:1191–1205PubMedCrossRefGoogle Scholar
  125. Zhou W, Chang S, Aune TM (2004) Long-range histone acetylation of the Ifng gene is an essential feature of T cell differentiation. Proc Natl Acad Sci U S A 101:2440–2445PubMedCrossRefGoogle Scholar
  126. Zhou Y, Yuan J, Pan Y, Fei Y, Qiu X, Hu N, Luo Y, Lei W, Li Y, Long H, Sawalha AH, Richardson B, Lu Q (2009) T cell CD40LG gene expression and the production of IgG by autologous B cells in systemic lupus erythematosus. Clin Immunol 132:362–370PubMedCrossRefGoogle Scholar
  127. Zhu J, Paul WE (2008) CD4 T cells: fates, functions, and faults. Blood 112:1557–1569PubMedCrossRefGoogle Scholar
  128. Zhu J, Guo L, Watson CJ, Hu-Li J, Paul WE (2001) Stat6 is necessary and sufficient for IL-4’s role in Th2 differentiation and cell expansion. J Immunol 166:7276–7281PubMedGoogle Scholar
  129. Zhu J, Cote-Sierra J, Guo L, Paul WE (2003) Stat5 activation plays a critical role in Th2 differentiation. Immunity 19:739–748PubMedCrossRefGoogle Scholar
  130. Zhu J, Min B, Hu-Li J, Watson CJ, Grinberg A, Wang Q, Killeen N, Urban JF Jr, Guo L, Paul WE (2004) Conditional deletion of Gata3 shows its essential function in T(H)1-T(H)2 responses. Nat Immunol 5:1157–1165PubMedCrossRefGoogle Scholar
  131. Zhu J, Yamane H, Paul WE (2010) Differentiation of effector CD4 T cell populations (*). Annu Rev Immunol 28:445–489PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Laboratory for Functional GenomicsFondation Jean Dausset – Centre d’Etude du Polymorphisme Humain (CEPH)ParisFrance
  2. 2.Laboratory for Epigenetics, Centre National de GénotypageCEA-Institut de GénomiqueEvryFrance

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