Skip to main content
SpringerLink
Log in

Epigenetic Changes in Inflammatory and Autoimmune Diseases

  • Chapter
  • First Online:
Epigenetics: Development and Disease

Part of the book series: Subcellular Biochemistry ((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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • 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 3:549–557

    Article  PubMed  CAS  Google Scholar 

  • Aho K, Koskenvuo M, Tuominen J, Kaprio J (1986) Occurrence of rheumatoid arthritis in a nationwide series of twins. J Rheumatol 13:899–902

    PubMed  CAS  Google Scholar 

  • Ansel KM, Lee DU, Rao A (2003) An epigenetic view of helper T cell differentiation. Nat Immunol 4:616–623

    Article  PubMed  CAS  Google Scholar 

  • Ansel KM, Djuretic I, Tanasa B, Rao A (2006) Regulation of Th2 differentiation and Il4 locus accessibility. Annu Rev Immunol 24:607–656

    Article  PubMed  CAS  Google Scholar 

  • 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 52:267–277

    Article  PubMed  CAS  Google Scholar 

  • Ashkenazi A, Dixit VM (1998) Death receptors: signaling and modulation. Science 281:1305–1308

    Article  PubMed  CAS  Google Scholar 

  • Aune TM, Collins PL, Chang S (2009) Epigenetics and T helper 1 differentiation. Immunology 126:299–305

    Article  PubMed  CAS  Google Scholar 

  • 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 3:643–651

    Article  PubMed  CAS  Google Scholar 

  • 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 179:572–578

    Article  PubMed  CAS  Google Scholar 

  • 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 101:11410–11415

    Article  PubMed  CAS  Google Scholar 

  • 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 33:35–47

    Article  PubMed  CAS  Google Scholar 

  • Ballestar E (2010) Epigenetics lessons from twins: prospects for autoimmune disease. Clin Rev Allergy Immunol 39:30–41

    Article  PubMed  CAS  Google Scholar 

  • 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 129:823–837

    Article  PubMed  CAS  Google Scholar 

  • 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 131:1853–1860

    Article  PubMed  CAS  Google Scholar 

  • 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 132:311–322

    Article  PubMed  CAS  Google Scholar 

  • 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 128:618–625

    Article  PubMed  CAS  Google Scholar 

  • 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 279:41249–41257

    Article  PubMed  CAS  Google Scholar 

  • Brooks WH (2010) X chromosome inactivation and autoimmunity. Clin Rev Allergy Immunol 39:20–29

    Article  PubMed  Google Scholar 

  • Buckner JH (2010) Mechanisms of impaired regulation by CD4(+)CD25(+)FOXP3(+) regulatory T cells in human autoimmune diseases. Nat Rev Immunol 10:849–859

    Article  PubMed  CAS  Google Scholar 

  • Calvanese V, Lara E, Kahn A, Fraga MF (2009) The role of epigenetics in aging and age-related diseases. Ageing Res Rev 8:268–276

    Article  PubMed  CAS  Google Scholar 

  • 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 8:723–731

    Article  PubMed  CAS  Google Scholar 

  • 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 566:481–491

    Article  PubMed  CAS  Google Scholar 

  • 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 170:141–147

    Article  PubMed  Google Scholar 

  • 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 8:145–153

    Article  PubMed  CAS  Google Scholar 

  • Durrant DM, Metzger DW (2010) Emerging roles of T helper subsets in the pathogenesis of asthma. Immunol Invest 39:526–549

    Article  PubMed  CAS  Google Scholar 

  • Eizirik DL, Colli ML, Ortis F (2009) The role of inflammation in insulitis and beta-cell loss in type 1 diabetes. Nat Rev Endocrinol 5:219–226

    Article  PubMed  CAS  Google Scholar 

  • 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 169:647–650

    PubMed  CAS  Google Scholar 

  • Firestein GS (2003) Evolving concepts of rheumatoid arthritis. Nature 423:356–361

    Article  PubMed  CAS  Google Scholar 

  • Fraga MF (2009) Genetic and epigenetic regulation of aging. Curr Opin Immunol 21:446–453

    Article  PubMed  CAS  Google Scholar 

  • 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 102:10604–10609

    Article  PubMed  CAS  Google Scholar 

  • 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 176:5015–5022

    PubMed  CAS  Google Scholar 

  • 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 14:205–215

    Article  PubMed  CAS  Google Scholar 

  • 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 179:6410–6415

    PubMed  CAS  Google Scholar 

  • 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 25:717–729

    Article  PubMed  CAS  Google Scholar 

  • 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 174:134–141

    Article  PubMed  CAS  Google Scholar 

  • Holliday R (2006) Epigenetics: a historical overview. Epigenetics 1:76–80

    Article  PubMed  Google Scholar 

  • 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 56:1087–1093

    Article  PubMed  CAS  Google Scholar 

  • 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 10:81–91

    Article  PubMed  CAS  Google Scholar 

  • Ivanov II, Zhou L, Littman DR (2007) Transcriptional regulation of Th17 cell differentiation. Semin Immunol 19:409–417

    Article  PubMed  CAS  Google Scholar 

  • 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 20:170–179

    Article  PubMed  CAS  Google Scholar 

  • Karouzakis E, Gay RE, Michel BA, Gay S, Neidhart M (2009) DNA hypomethylation in rheumatoid arthritis synovial fibroblasts. Arthritis Rheum 60:3613–3622

    Article  PubMed  CAS  Google Scholar 

  • Kimura A, Kishimoto T (2010) IL-6: regulator of Treg/Th17 balance. Eur J Immunol 40:1830–1835

    Article  PubMed  CAS  Google Scholar 

  • 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 112:2340–2352

    Article  PubMed  CAS  Google Scholar 

  • Kouzarides T (2007) Chromatin modifications and their function. Cell 128:693–705

    Article  PubMed  CAS  Google Scholar 

  • 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 280:31470–31477

    Article  PubMed  CAS  Google Scholar 

  • Kristensen LS, Nielsen HM, Hansen LL (2009) Epigenetics and cancer treatment. Eur J Pharmacol 625:131–142

    Article  PubMed  CAS  Google Scholar 

  • Krueger GG, Duvic M (1994) Epidemiology of psoriasis: clinical issues. J Invest Dermatol 102:14S–18S

    Article  PubMed  CAS  Google Scholar 

  • 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 186:4388–4395

    Article  PubMed  CAS  Google Scholar 

  • Larche M (2007) Regulatory T cells in allergy and asthma. Chest 132:1007–1014

    Article  PubMed  CAS  Google Scholar 

  • 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 5:589–595

    Article  PubMed  CAS  Google Scholar 

  • 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 172:921–929

    Article  PubMed  Google Scholar 

  • Lee DU, Agarwal S, Rao A (2002) Th2 lineage commitment and efficient IL-4 production involves extended demethylation of the IL-4 gene. Immunity 16:649–660

    Article  PubMed  CAS  Google Scholar 

  • 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 279:4802–4810

    Article  PubMed  CAS  Google Scholar 

  • 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 26:1292–1302

    Article  PubMed  CAS  Google Scholar 

  • 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 98:15137–15142

    Article  PubMed  CAS  Google Scholar 

  • 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 150:862–872

    Article  PubMed  CAS  Google Scholar 

  • 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 102:76–81

    Article  PubMed  CAS  Google Scholar 

  • 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 135:96–99

    Article  PubMed  CAS  Google Scholar 

  • 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 288:136–140

    Article  PubMed  CAS  Google Scholar 

  • 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 179:6352–6358

    PubMed  CAS  Google Scholar 

  • Lucey DR, Clerici M, Shearer GM (1996) Type 1 and type 2 cytokine dysregulation in human infectious, neoplastic, and inflammatory diseases. Clin Microbiol Rev 9:532–562

    PubMed  CAS  Google Scholar 

  • 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 4:1183–1190

    Article  PubMed  CAS  Google Scholar 

  • 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 85:2006–2016

    Article  PubMed  CAS  Google Scholar 

  • McGeachy MJ, Cua DJ (2008) Th17 cell differentiation: the long and winding road. Immunity 28:445–453

    Article  PubMed  CAS  Google Scholar 

  • McGee HS, Agrawal DK (2006) TH2 cells in the pathogenesis of airway remodeling: regulatory T cells a plausible panacea for asthma. Immunol Res 35:219–232

    Article  PubMed  CAS  Google Scholar 

  • Meda F, Folci M, Baccarelli A, Selmi C (2011) The epigenetics of autoimmunity. Cell Mol Immunol 8:226–236

    Article  PubMed  CAS  Google Scholar 

  • 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 57:3189–3198

    Article  PubMed  CAS  Google Scholar 

  • 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 22:2980–2993

    Article  PubMed  CAS  Google Scholar 

  • 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 98:2628–2633

    Article  PubMed  CAS  Google Scholar 

  • Moscarello MA, Wood DD, Ackerley C, Boulias C (1994) Myelin in multiple sclerosis is developmentally immature. J Clin Invest 94:146–154

    Article  PubMed  CAS  Google Scholar 

  • Mottet C, Uhlig HH, Powrie F (2003) Cutting edge: cure of colitis by CD4  +  CD25+ regulatory T cells. J Immunol 170:3939–3943

    PubMed  CAS  Google Scholar 

  • Murdaca G, Colombo BM, Puppo F (2011) The role of Th17 lymphocytes in the autoimmune and chronic inflammatory diseases. Intern Emerg Med 6:487–495

    Article  PubMed  Google Scholar 

  • Murphy KM, Reiner SL (2002) The lineage decisions of helper T cells. Nat Rev Immunol 2:933–944

    Article  PubMed  CAS  Google Scholar 

  • 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 7:443–452

    Article  PubMed  CAS  Google Scholar 

  • 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):e810

    Google Scholar 

  • 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 204:1749–1755

    Article  PubMed  CAS  Google Scholar 

  • Nardone J, Lee DU, Ansel KM, Rao A (2004) Bioinformatics for the ‘bench biologist’: how to find regulatory regions in genomic DNA. Nat Immunol 5:768–774

    Article  PubMed  CAS  Google Scholar 

  • 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 43:2634–2647

    Article  PubMed  CAS  Google Scholar 

  • 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 50:3365–3376

    Article  PubMed  CAS  Google Scholar 

  • 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 12:27–37

    Article  PubMed  CAS  Google Scholar 

  • Ouyang W, Kolls JK, Zheng Y (2008) The biological functions of T helper 17 cell effector cytokines in inflammation. Immunity 28:454–467

    Article  PubMed  CAS  Google Scholar 

  • 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 101:1993–1998

    Article  PubMed  CAS  Google Scholar 

  • 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 184:6773–6781

    Article  PubMed  CAS  Google Scholar 

  • 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:e4488

    Article  PubMed  CAS  Google Scholar 

  • Placek K, Coffre M, Maiella S, Bianchi E, Rogge L (2009) Genetic and epigenetic networks controlling T helper 1 cell differentiation. Immunology 127:155–162

    Article  PubMed  CAS  Google Scholar 

  • 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 93:14002–14007

    Article  PubMed  CAS  Google Scholar 

  • 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 31:123–130

    Article  PubMed  CAS  Google Scholar 

  • 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 182:999–1010

    PubMed  CAS  Google Scholar 

  • 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 17:456–470

    Article  PubMed  CAS  Google Scholar 

  • 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 33:1665–1673

    Article  PubMed  CAS  Google Scholar 

  • 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 326:298–304

    Article  PubMed  CAS  Google Scholar 

  • 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 212:8–27

    Article  PubMed  CAS  Google Scholar 

  • Sakaguchi S, Yamaguchi T, Nomura T, Ono M (2008) Regulatory T cells and immune tolerance. Cell 133:775–787

    Article  PubMed  CAS  Google Scholar 

  • Sawalha AH, Harley JB (2004) Antinuclear autoantibodies in systemic lupus erythematosus. Curr Opin Rheumatol 16:534–540

    Article  PubMed  Google Scholar 

  • 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 8:732–742

    Article  PubMed  CAS  Google Scholar 

  • Selmi C (2009) What is hot in autoimmunity. Acta Reumatol Port 34:580–588

    PubMed  Google Scholar 

  • Selvi BR, Mohankrishna DV, Ostwal YB, Kundu TK (2010) Small molecule modulators of histone acetylation and methylation: a disease perspective. Biochim Biophys Acta 1799:810–828

    Article  PubMed  CAS  Google Scholar 

  • 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 25:208–218

    Article  PubMed  CAS  Google Scholar 

  • 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 101:12622–12627

    Article  PubMed  CAS  Google Scholar 

  • Soto ME, Vallejo M, Guillen F, Simon JA, Arena E, Reyes PA (2004) Gender impact in systemic lupus erythematosus. Clin Exp Rheumatol 22:713–721

    PubMed  CAS  Google Scholar 

  • 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 4:1521–1532

    Article  PubMed  CAS  Google Scholar 

  • 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 54:779–787

    Article  PubMed  CAS  Google Scholar 

  • 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 10:1981–1985

    Article  PubMed  CAS  Google Scholar 

  • 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 13:1299–1307

    Article  PubMed  CAS  Google Scholar 

  • Taylor A, Verhagen J, Akdis CA, Akdis M (2005) T regulatory cells and allergy. Microbes Infect 7:1049–1055

    Article  PubMed  CAS  Google Scholar 

  • 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 29:679–690

    Article  PubMed  CAS  Google Scholar 

  • Tost J (2008) Epigenetics. Caister Academic Press, Norfolk, UK

    Google Scholar 

  • Tsaprouni LG, Ito K, Powell JJ, Adcock IM, Punchard N (2011) Differential patterns of histone acetylation in inflammatory bowel diseases. J Inflamm (Lond) 8:1

    Article  CAS  Google Scholar 

  • 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 280:28177–28185

    Article  PubMed  CAS  Google Scholar 

  • 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 18:415–428

    Article  PubMed  CAS  Google Scholar 

  • 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 203:755–766

    Article  PubMed  CAS  Google Scholar 

  • 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 80:1816–1832

    Article  CAS  Google Scholar 

  • 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 25:821–852

    Article  PubMed  CAS  Google Scholar 

  • 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 30:155–167

    Article  PubMed  CAS  Google Scholar 

  • Whitelaw NC, Whitelaw E (2006) How lifetimes shape epigenotype within and across generations. Hum Mol Genet 15(Spec No 2):R131–137

    Google Scholar 

  • Wilson CB, Rowell E, Sekimata M (2009) Epigenetic control of T-helper-cell differentiation. Nat Rev Immunol 9:91–105

    Article  PubMed  CAS  Google Scholar 

  • 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 3:42–47

    Article  PubMed  CAS  Google Scholar 

  • 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 277:42399–42408

    Article  PubMed  CAS  Google Scholar 

  • 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 24:611–622

    Article  PubMed  CAS  Google Scholar 

  • 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 110:2494–2500

    Article  PubMed  CAS  Google Scholar 

  • 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 28:29–39

    Article  PubMed  CAS  Google Scholar 

  • 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 35:58–69

    Article  PubMed  CAS  Google Scholar 

  • 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:R227

    Article  PubMed  CAS  Google Scholar 

  • 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 87:1191–1205

    Article  PubMed  CAS  Google Scholar 

  • 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 101:2440–2445

    Article  PubMed  CAS  Google Scholar 

  • 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 132:362–370

    Article  PubMed  CAS  Google Scholar 

  • Zhu J, Paul WE (2008) CD4 T cells: fates, functions, and faults. Blood 112:1557–1569

    Article  PubMed  CAS  Google Scholar 

  • 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 166:7276–7281

    PubMed  CAS  Google Scholar 

  • Zhu J, Cote-Sierra J, Guo L, Paul WE (2003) Stat5 activation plays a critical role in Th2 differentiation. Immunity 19:739–748

    Article  PubMed  CAS  Google Scholar 

  • 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 5:1157–1165

    Article  PubMed  CAS  Google Scholar 

  • Zhu J, Yamane H, Paul WE (2010) Differentiation of effector CD4 T cell populations (*). Annu Rev Immunol 28:445–489

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory for Functional Genomics, Fondation Jean Dausset – Centre d’Etude du Polymorphisme Humain (CEPH), 27 rue Juliette Dodu, 75010, Paris, France

    Helene Myrtue Nielsen & Jörg Tost Ph.D.

  2. Laboratory for Epigenetics, Centre National de Génotypage, CEA-Institut de Génomique, Bâtiment G2, 2 rue Gaston Crémieux, CP 5721, 91000, Evry, France

    Jörg Tost Ph.D.

Authors
  1. Helene Myrtue Nielsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jörg Tost Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jörg Tost Ph.D. .

Editor information

Editors and Affiliations

  1. Advanced Scientific Research, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for, Jakkur P.O., Bangalore, 560064, India

    Tapas K. Kundu

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Nielsen, H.M., Tost, J. (2013). Epigenetic Changes in Inflammatory and Autoimmune Diseases. In: Kundu, T. (eds) Epigenetics: Development and Disease. Subcellular Biochemistry, vol 61. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4525-4_20

Download citation

Publish with us

Policies and ethics

Search

Navigation