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Epigenetic alterations and autoimmune disease

Published online by Cambridge University Press:  09 August 2011

Y. Renaudineau ,
D. Beauvillard ,
M. Padelli ,
W. H. Brooks  and
P. Youinou
Y. Renaudineau*
Affiliation:
Laboratory of Immunology, Brest University Medical School, CHU Morvan, Brest, France EA2216 Immunology and Pathology, IFR 148 Scin Bios, Université Européenne de Bretagne, Brest, France
D. Beauvillard
Affiliation:
Laboratory of Immunology, Brest University Medical School, CHU Morvan, Brest, France
M. Padelli
Affiliation:
Laboratory of Immunology, Brest University Medical School, CHU Morvan, Brest, France
W. H. Brooks
Affiliation:
Experimental HTS, Drug Discovery Department, Mofitt Cancer Center, Tampa, FL, USA
P. Youinou
Affiliation:
Laboratory of Immunology, Brest University Medical School, CHU Morvan, Brest, France EA2216 Immunology and Pathology, IFR 148 Scin Bios, Université Européenne de Bretagne, Brest, France
*
*Address for correspondence: Y. Renaudineau, Pharm.D., Ph.D., Laboratory of Immunology, Brest University Medical School Hospital, BP824, F-29609 Brest, France. (Email [email protected])
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Abstract

Recent advances in epigenetics have enhanced our knowledge of how environmental factors (UV radiation, drugs, infections, etc.) contribute to the development of autoimmune diseases (AID) in genetically predisposed individuals. Studies conducted in monozygotic twins discordant for AID and spontaneous autoimmune animal models have highlighted the importance of DNA methylation changes and histone modifications. Alterations in the epigenetic pattern seem to be cell specific, as CD4+ T cells and B cells are dysregulated in systemic lupus erythematosus, synovial fibroblasts in rheumatoid arthritis and cerebral cells in multiple sclerosis. With regard to lymphocytes, the control of tolerance is affected, leading to the development of autoreactive cells. Other epigenetic processes, such as the newly described miRNAs, and post-translational protein modifications may also be suspected. Altogether, a conceptual revolution is in progress, in AID, with potential new therapeutic strategies targeting epigenetic patterns.

Keywords

autoimmune diseasesDNA methylationepigeneticslymphocytemiRNA
Type
Review
Information
Journal of Developmental Origins of Health and Disease , Volume 2 , Issue 5 , October 2011 , pp. 258 - 264
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2011

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References

1.Shapira, Y, Agmon-Levin, N, Shoenfeld, Y. Defining and analyzing geoepidemiology and human autoimmunity. J Autoimmun. 2010; 34, J168–J177.Google Scholar
2.Youinou, P. Conference scene: highlights of the 7th Autoimmunity Congress. Immunotherapy. 2010; 2, 611–617.CrossRefGoogle ScholarPubMed
3.Sirota, M, Schaub, MA, Batzoglou, S, Robinson, WH, Butte, AJ. Autoimmune disease classification by inverse association with SNP alleles. PLoS Genet. 2009; 5, e1000792.Google Scholar
4.Ballestar, E. Epigenetics lessons from twins: prospects for autoimmune disease. Clin Rev Allergy Immunol. 2010; 39, 30–41.CrossRefGoogle ScholarPubMed
5.Brooks, WH, Le Dantec, C, Pers, JO, Youinou, P, Renaudineau, Y. Epigenetics and autoimmunity. J Autoimmun. 2010; 34, J207–J219.CrossRefGoogle ScholarPubMed
6.Chang, C, Gershwin, ME. Drugs and autoimmunity: a contemporary review and mechanistic approach. J Autoimmun. 2010; 34, J266–J275.CrossRefGoogle ScholarPubMed
7.Yuan, BZ, Jefferson, AM, Popescu, NC, Reynolds, SH. Aberrant gene expression in human non small cell lung carcinoma cells exposed to demethylating agent 5-aza-2′-deoxycytidine. Neoplasia. 2004; 6, 412–419.Google Scholar
8.Bhutani, N, Brady, JJ, Damian, M, et al. . Reprogramming towards pluripotency requires AID-dependent DNA demethylation. Nature. 2010; 463, 1042–1047.CrossRefGoogle ScholarPubMed
9.Popp, C, Dean, W, Feng, S, et al. . Genome-wide erasure of DNA methylation in mouse primordial germ cells is affected by AID deficiency. Nature. 2010; 463, 1101–1105.CrossRefGoogle ScholarPubMed
10.Dieker, J, Muller, S. Epigenetic histone code and autoimmunity. Clin Rev Allergy Immunol. 2010; 39, 78–84.Google Scholar
11.Cannat, A, Seligmann, M. Induction by isoniazid and hydralazine of antinuclear factors in mice. Clin Exp Immunol. 1968; 3, 99–105.Google Scholar
12.Yoshida, H, Yoshida, M, Merino, R, Shibata, T, Izui, S. 5-Azacytidine inhibits the lpr gene-induced lymphadenopathy and acceleration of lupus-like syndrome in MRL/MpJ-lpr/lpr mice. Eur J Immunol. 1990; 20, 1989–1993.Google Scholar
13.Quddus, J, Johnson, KJ, Gavalchin, J, et al. . Treating activated CD4+ T cells with either of two distinct DNA methyltransferase inhibitors, 5-azacytidine or procainamide, is sufficient to cause a lupus-like disease in syngeneic mice. J Clin Invest. 1993; 92, 38–53.Google Scholar
14.Mazari, L, Ouarzane, M, Zouali, M. Subversion of B lymphocyte tolerance by hydralazine, a potential mechanism for drug-induced lupus. Proc Natl Acad Sci U S A. 2007; 104, 6317–6322.CrossRefGoogle ScholarPubMed
15.Corvetta, A, Della Bitta, R, Luchetti, MM, Pomponio, G. 5-Methylcytosine content of DNA in blood, synovial mononuclear cells and synovial tissue from patients affected by autoimmune rheumatic diseases. J Chromatogr. 1991; 566, 481–491.Google Scholar
16.Javierre, BM, Fernandez, AF, Richter, J, et al. . Changes in the pattern of DNA methylation associate with twin discordance in systemic lupus erythematosus. Genome Res. 2010; 20, 170–179.Google Scholar
17.Karouzakis, E, Gay, RE, Michel, BA, Gay, S, Neidhart, M. DNA hypomethylation in rheumatoid arthritis synovial fibroblasts. Arthritis Rheum. 2009; 60, 3613–3622.Google Scholar
18.Mastronardi, FG, Noor, A, Wood, DD, Paton, T, Moscarello, MA. Peptidyl argininedeiminase 2 CpG island in multiple sclerosis white matter is hypomethylated. J Neurosci Res. 2007; 85, 2006–2016.CrossRefGoogle ScholarPubMed
19.Baranzini, SE, Mudge, J, van Velkinburgh, JC, et al. . Genome, epigenome and RNA sequences of monozygotic twins discordant for multiple sclerosis. Nature. 2010; 464, 1351–1356.CrossRefGoogle ScholarPubMed
20.Mitchell, MM, Lleo, A, Zammataro, L, et al. . Epigenetic investigation of variably X chromosome inactivated genes in monozygotic female twins discordant for primary biliary cirrhosis. Epigenetics. 2011; 6, 95–102.Google Scholar
21.Li, JZ, Steinman, CR. Plasma DNA in systemic lupus erythematosus. Characterization of cloned base sequences. Arthritis Rheum. 1989; 32, 726–733.Google Scholar
22.Balada, E, Ordi-Ros, J, Vilardell-Tarrés, M. Molecular mechanisms mediated by human endogenous retroviruses (HERVs) in autoimmunity. Rev Med Virol. 2009; 19, 273–286.Google Scholar
23.Pullmann, R Jr, Bonilla, E, Phillips, PE, Middleton, FA, Perl, A. Haplotypes of the HRES-1 endogenous retrovirus are associated with development and disease manifestations of systemic lupus erythematosus. Arthritis Rheum. 2008; 58, 532–540.CrossRefGoogle ScholarPubMed
24.Tai, AK, O'Reilly, EJ, Alroy, KA, et al. . Human endogenous retrovirus-K18 Env as a risk factor in multiple sclerosis. Mult Scler. 2008; 14, 1175–1180.Google Scholar
25.Marguerat, S, Wang, WY, Todd, JA, Conrad, B. Association of human endogenous retrovirus K-18 polymorphisms with type 1 diabetes. Diabetes. 2004; 53, 852–854.CrossRefGoogle ScholarPubMed
26.Tsuchiya, T, Saëgusa, Y, Taira, T, et al. . Ku antigen binds to Alu family DNA. J Biochem. 1998; 123, 120–127.Google Scholar
27.Gergely, P Jr, Pullmann, R, Stancato, C, et al. . Increased prevalence of transfusion-transmitted virus and cross-reactivity with immunodominant epitopes of the HRES-1/p28 endogenous retroviral autoantigen in patients with systemic lupus erythematosus. Clin Immunol. 2005; 116, 124–134.Google Scholar
28.Perron, H, Lang, A. The human endogenous retrovirus link between genes and environment in multiple sclerosis and in multifactorial diseases associating neuroinflammation. Clin Rev Allergy Immunol. 2010; 39, 51–61.Google Scholar
29.Renaudineau, Y, Vallet, S, Le Dantec, C, et al. . Characterization of the human CD5 endogenous retrovirus-E in B lymphocytes. Genes Immun. 2005; 6, 663–671.CrossRefGoogle ScholarPubMed
30.Weishaupt, H, Sigvardsson, M, Attema, JL. Epigenetic chromatin states uniquely define the developmental plasticity of murine hematopoietic stem cells. Blood. 2010; 115, 247–256.CrossRefGoogle ScholarPubMed
31.Attema, JL, Papathanasiou, P, Forsberg, EC, et al. . Epigenetic characterization of hematopoietic stem cell differentiation using miniChIP and bisulfite sequencing analysis. Proc Natl Acad Sci U S A. 2007; 104, 12371–12376.Google Scholar
32.Blanco-Betancourt, CE, Moncla, A, Milili, M, et al. . Defective B-cell-negative selection and terminal differentiation in the ICF syndrome. Blood. 2004; 103, 2683–2690.Google Scholar
33.Lu, Q, Renaudineau, Y, Cha, S, et al. . Epigenetics in autoimmune disorders: highlights of the 10th Sjögren's syndrome symposium. Autoimmun Rev. 2010; 9, 627–630.Google Scholar
34.Garaud, S, Le Dantec, C, Jousse-Joulin, S, et al. . IL-6 modulates CD5 expression in B cells from patients with lupus by regulating DNA methylation. J Immunol. 2009; 182, 5623–5632.CrossRefGoogle Scholar
35.Gorelik, G, Fang, JY, Wu, A, Sawalha, AH, Richardson, B. Impaired T cell protein kinase C delta activation decreases ERK pathway signaling in idiopathic and hydralazine-induced lupus. J Immunol. 2007; 179, 5553–5563.Google Scholar
36.Miyamoto, A, Nakayama, K, Imaki, H, et al. . Increased proliferation of B cells and auto-immunity in mice lacking protein kinase C delta. Nature. 2002; 416, 865–869.Google Scholar
37.Balada, E, Ordi-Ros, J, Serrano-Acedo, S, et al. . Transcript levels of DNA methyltransferases DNMT1, DNMT3A and DNMT3B in CD4+ T cells from patients with systemic lupus erythematosus. Immunology. 2008; 124, 339–347.Google Scholar
38.Liu, C, Ou, T, Wu, C, et al. . Global DNA methylation, DNMT1, and MBD2 in patients with systemic lupus erythematosus. Lupus. 2011; 20, 131–136.CrossRefGoogle ScholarPubMed
39.Grolleau-Julius, A, Ray, D, Yung, RL. The role of epigenetics in aging and autoimmunity. Clin Rev Allergy Immunol. 2010; 39, 42–50.Google Scholar
40.Rai, K, Huggins, IJ, James, SR, et al. . DNA demethylation in zebrafish involves the coupling of a deaminase, a glycosylase, and gadd45. Cell. 2008; 135, 1201–1212.Google Scholar
41.Balada, E, Ordi-Ros, J, Serrano-Acedo, S, et al. . Transcript overexpression of the MBD2 and MBD4 genes in CD4+ T cells from systemic lupus erythematosus patients. J Leukoc Biol. 2007; 81, 1609–1616.Google Scholar
42.Li, Y, Zhao, M, Yin, H, et al. . Overexpression of the growth arrest and DNA damage-induced 45alpha gene contributes to autoimmunity by promoting DNA demethylation in lupus T cells. Arthritis Rheum. 2010; 62, 1438–1447.Google Scholar
43.Tatemichi, M, Hata, H, Nakadate, T. Ectopic expression of activation-induced cytidine deaminase caused by epigenetics modification. Oncol Rep. 2011; 25, 153–158.Google ScholarPubMed
44.Jiang, C, Foley, J, Clayton, N, et al. . Abrogation of lupus nephritis in activation-induced deaminase-deficient MRL/lpr mice. J Immunol. 2007; 178, 7422–7431.CrossRefGoogle ScholarPubMed
45.Li, Y, Liu, Y, Strickland, FM, Richardson, B. Age-dependent decreases in DNA methyltransferase levels and low transmethylation micronutrient levels synergize to promote overexpression of genes implicated in autoimmunity and acute coronary syndromes. Exp Gerontol. 2010; 45, 312–322.CrossRefGoogle ScholarPubMed
46.Brooks, WH. X chromosome inactivation and autoimmunity. Clin Rev Allergy Immunol. 2010; 39, 20–29.CrossRefGoogle ScholarPubMed
47.Claverie, N, Pasquali, JL, Mamont, PS, et al. . Immunosuppressive effects of (2R,5R)-6-heptyne-2,5-diamine, an inhibitor of polyamine synthesis: II. Beneficial effects on the development of a lupus-like disease in MRL-lpr/lpr mice. Clin Exp Immunol. 1988; 72, 293–298.Google Scholar
48.Puri, H, Campell, RA, Puri-Harner, V, et al. . Serum free polyamines in children with systemic lupus erythmeatosus. Adv Polyamine Res. 1978; 2, 359–367.Google Scholar
49.Furumitsu, Y, Yukioka, K, Yukioka, M, et al. . Interleukin-1beta induces elevation of spermidine/spermine N1-acetyltransferase activity and an increase in the amount of putrescine in synovial adherent cells from patients with rheumatoid arthritis. J Rheumatol. 2000; 27, 1352–1357.Google Scholar
50.Yukioka, K, Wakitani, S, Yukioka, M, et al. . Polyamine levels in synovial tissues and synovial fluids of patients with rheumatoid arthritis. J Rheumatol. 1992; 19, 689–692.Google ScholarPubMed
51.Bajaj, BG, Murakami, M, Cai, Q, et al. . Epstein–Barr virus nuclear antigen 3C interacts with and enhances the stability of the c-Myc oncoprotein. J Virol. 2008; 82, 4082–4090.CrossRefGoogle ScholarPubMed
52.Brooks, WH, McCloskey, DE, Daniel, KG, et al. . In silico chemical library screening and experimental validation of a novel 9-aminoacridine based lead-inhibitor of human S-adenosylmethionine decarboxylase. J Chem Inf Model. 2007; 47, 1897–1905.Google Scholar
53.Hu, N, Qiu, X, Luo, Y, et al. . Abnormal histone modification patterns in lupus CD4+ T cells. J Rheumatol. 2008; 35, 804–810.Google ScholarPubMed
54.Lu, ZP, Ju, ZL, Shi, GY, Zhang, JW, Sun, J. Histone deacetylase inhibitor Trichostatin A reduces anti-DNA autoantibody production and represses IgH gene transcription. Biochem Biophys Res Commun. 2005; 330, 204–209.Google Scholar
55.Salvi, V, Bosisio, D, Mitola, S, et al. . Trichostatin A blocks type I interferon production by activated plasmacytoid dendritic cells. Immunobiology. 2010; 215, 756–761.CrossRefGoogle ScholarPubMed
56.Reilly, CM, Thomas, M, Gogal, R Jr, et al. . The histone deacetylase inhibitor trichostatin A upregulates regulatory T cells and modulates autoimmunity in NZB/W F1 mice. J Autoimmun. 2008; 31, 123–130, 1897–1905.Google Scholar
57.Xiao, C, Srinivasan, L, Calado, DP, et al. . Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes. Nat Immunol. 2008; 9, 405–414.CrossRefGoogle ScholarPubMed
58.Pan, W, Zhu, S, Yuan, M, et al. . MicroRNA-21 and microRNA-148a contribute to DNA hypomethylation in lupus CD4+ T cells by directly and indirectly targeting DNA methyltransferase 1. J Immunol. 2010; 184, 6773–6781.Google Scholar
59.Zhao, S, Wang, Y, Liang, Y, et al. . MicroRNA-126 regulates DNA methylation in CD4(+) T cells and contributes to systemic lupus erythematosus by targeting DNA methyltransferase 1. Arthritis Rheum. 2010; 63, 1376–1386.CrossRefGoogle Scholar
60.Noonan, EJ, Place, RF, Pookot, D, et al. . miR-449a targets HDAC-1 and induces growth arrest in prostate cancer. Oncogene. 2009; 28, 1714–1724.CrossRefGoogle ScholarPubMed
61.Chen, Y, Luo, J, Tian, R, Sun, H, Zou, S. miR-373 negatively regulates methyl-CpG-binding domain protein 2 (MBD2) in hilar cholangiocarcinoma. Dig Dis Sci. 2011; 56, 1693–1701.CrossRefGoogle ScholarPubMed
62.Divekar, AA, Dubey, S, Gangalum, PR, Singh, RR. Dicer insufficiency and microRNA-155 overexpression in lupus regulatory T cells: an apparent paradox in the setting of an inflammatory milieu. J Immunol. 2011; 186, 924–930.CrossRefGoogle ScholarPubMed
63.Stanczyk, J, Pedrioli, DM, Brentano, F, et al. . Altered expression of microRNA in synovial fibroblasts and synovial tissue in rheumatoid arthritis. Arthritis Rheum. 2008; 58, 1001–1009.Google Scholar
64.Chan, EK, Satoh, M, Pauley, KM. Contrast in aberrant microRNA expression in systemic lupus erythematosus and rheumatoid arthritis: is microRNA-146 all we need? Arthritis Rheum. 2009; 60, 912–915.Google Scholar
65.Saito, Y, Friedman, JM, Chihara, Y, et al. . Epigenetic therapy upregulates the tumor suppressor microRNA-126 and its host gene EGFL7 in human cancer cells. Biochem Biophys Res Commun. 2009; 379, 726–731.Google Scholar
66.Cuthbert, GL, Daujat, S, Snowden, AW, et al. . Histone deimination antagonizes arginine methylation. Cell. 2004; 118, 545–553.CrossRefGoogle ScholarPubMed
67.Wegner, N, Wait, R, Sroka, A, et al. . Peptidylarginine deiminase from Porphyromonas gingivalis citrullinates human fibrinogen and α-enolase: implications for autoimmunity in rheumatoid arthritis. Arthritis Rheum. 2010; 62, 2662–2672.Google Scholar
68.Mastronardi, FG, Noor, A, Wood, DD, Paton, T, Moscarello, MA. Peptidyl argininedeiminase 2 CpG island in multiple sclerosis white matter is hypomethylated. J Neurosci Res. 2007; 85, 2006–2016.Google Scholar
69.Kang, HK, Chiang, MY, Liu, M, Ecklund, D, Datta, SK. The histone peptide H4(71–94) alone is more effective than a cocktail of peptide epitopes in controlling lupus: immunoregulatory mechanisms. J Clin Immunol. 2011; doi:10.1007/s 10875-010-9504-4.CrossRefGoogle ScholarPubMed
70.Garaud, S, Le Dantec, C, Berthou, C, et al. . Selection of the alternative exon 1 from the cd5 gene down-regulates membrane level of the protein in B lymphocytes. J Immunol. 2008; 181, 2010–2018.Google Scholar
71.Renaudineau, Y, Hillion, S, Saraux, A, Mageed, RA, Youinou, P. An alternative exon 1 of the CD5 gene regulates CD5 expression in human B lymphocytes. Blood. 2005; 106, 2781–2789.Google Scholar
72.Hewagama, A, Richardson, B. The genetics and epigenetics of autoimmune diseases. J Autoimmun. 2009; 33, 3–11.Google Scholar