Epigenetics in autoimmune diseases: Pathogenesis and prospects for therapy

Autoimmunity Reviews

Volumn 14, Issue 10, 2015, Pages 854-863

  Zhang, Zimu ^a,b,c   Zhang, Rongxin ^a,b,c  

^a TIANJIN MEDICAL UNIVERSITY   (China)

^b Key Laboratory of Immune Microenvironments and Diseases of Educational Ministry of China   (China)

^c Metabolic Diseases Hospital   (China)

Author keywords

Autoimmune disease; DNA methylation; Epigenetic therapy; Epigenetics; Histone modification; ncRNA

Indexed keywords

LONG UNTRANSLATED RNA; MICRORNA; UNTRANSLATED RNA; HISTONE;

AUTOIMMUNE DISEASE; CLINICAL TRIAL (TOPIC); DNA METHYLATION; EPIGENETICS; HISTONE ACETYLATION; HISTONE METHYLATION; HISTONE MODIFICATION; HUMAN; LYMPHOCYTE; MOLECULAR INTERACTION; NONHUMAN; PATHOGENESIS; REVIEW; ACETYLATION; ANIMAL; GENETIC EPIGENESIS; GENETICS; METABOLISM;

ACETYLATION; ANIMALS; AUTOIMMUNE DISEASES; DNA METHYLATION; EPIGENESIS, GENETIC; HISTONES; HUMANS; MICRORNAS;

EID: 84940614381     PISSN: 15689972     EISSN: 18730183     Source Type: Journal    
DOI: 10.1016/j.autrev.2015.05.008     Document Type: Review

References (122)

1. Zhernakova A., Withoff S., Wijmenga C. Clinical implications of shared genetics and pathogenesis in autoimmune diseases. Nat Rev Endocrinol 2013, 9:646-659.
2. Anaya J.M., Gomez L., Castiblanco J. Is there a common genetic basis for autoimmune diseases?. Clin Dev Immunol 2006, 13:185-195.
3. Lie B.A., Thorsby E. Several genes in the extended human MHC contribute to predisposition to autoimmune diseases. Curr Opin Immunol 2005, 17:526-531.
4. Ballestar E. Epigenetics lessons from twins: prospects for autoimmune disease. Clin Rev Allergy Immunol 2010, 39:30-41.
5. Bird A. Perceptions of epigenetics. Nature 2007, 447:396-398.
6. Costenbader K.H., Gay S., Alarcon-Riquelme M.E., Iaccarino L., Doria A. Genes, epigenetic regulation and environmental factors: which is the most relevant in developing autoimmune diseases?. Autoimmun Rev 2012, 11:604-609.
7. Karlson E.W., Chang S.C., Cui J., Chibnik L.B., Fraser P.A., De Vivo I., et al. Gene-environment interaction between HLA-DRB1 shared epitope and heavy cigarette smoking in predicting incident rheumatoid arthritis. Ann Rheum Dis 2010, 69:54-60.
8. Hernan M.A., Olek M.J., Ascherio A. Cigarette smoking and incidence of multiple sclerosis. Am J Epidemiol 2001, 154:69-74.
9. Munger K.L., Levin L.I., Hollis B.W., Howard N.S., Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA 2006, 296:2832-2838.
10. Deane K.D., El-Gabalawy H. Pathogenesis and prevention of rheumatic disease: focus on preclinical RA and SLE. Nat Rev Rheumatol 2014, 10:212-228.
11. Guo H., Zhu P., Yan L., Li R., Hu B., Lian Y., et al. The DNA methylation landscape of human early embryos. Nature 2014, 511:606-610.
12. Ehrlich M., Lacey M. DNA methylation and differentiation: silencing, upregulation and modulation of gene expression. Epigenomics 2013, 5:553-568.
13. Arand J., Spieler D., Karius T., Branco M.R., Meilinger D., Meissner A., et al. In vivo control of CpG and non-CpG DNA methylation by DNA methyltransferases. PLoS Genet 2012, 8:e1002750.
14. Ooi S.K., Bestor T.H. The colorful history of active DNA demethylation. Cell 2008, 133:1145-1148.
15. Fritz E.L., Papavasiliou F.N. Cytidine deaminases: AIDing DNA demethylation?. Genes Dev 2010, 24:2107-2114.
16. Fritz E.L., Rosenberg B.R., Lay K., Mihailovic A., Tuschl T., Papavasiliou F.N. A comprehensive analysis of the effects of the deaminase AID on the transcriptome and methylome of activated B cells. Nat Immunol 2013, 14:749-755.
17. Detanico T., Guo W., Wysocki L.J. Predominant role for activation-induced cytidine deaminase in generating IgG anti-nucleosomal antibodies of murine SLE. J Autoimmun 2015, 58:67-77.
18. Richardson B., Scheinbart L., Strahler J., Gross L., Hanash S., Johnson M. Evidence for impaired T cell DNA methylation in systemic lupus erythematosus and rheumatoid arthritis. Arthritis Rheum 1990, 33:1665-1673.
19. Lei W., Luo Y., Yan K., Zhao S., Li Y., Qiu X., et al. Abnormal DNA methylation in CD4+ T cells from patients with systemic lupus erythematosus, systemic sclerosis, and dermatomyositis. Scand J Rheumatol 2009, 38:369-374.
20. Lu Q., Wu A., Tesmer L., Ray D., Yousif N., Richardson B. Demethylation of CD40LG on the inactive X in T cells from women with lupus. J Immunol 2007, 179:6352-6358.
21. Lian X., Xiao R., Hu X., Kanekura T., Jiang H., Li Y., et al. DNA demethylation of CD40l in CD4+ T cells from women with systemic sclerosis: a possible explanation for female susceptibility. Arthritis Rheum 2012, 64:2338-2345.
22. Liao J., Liang G., Xie S., Zhao H., Zuo X., Li F., et al. CD40L demethylation in CD4(+) T cells from women with rheumatoid arthritis. Clin Immunol 2012, 145:13-18.
23. Iezzi G., Sonderegger I., Ampenberger F., Schmitz N., Marsland B.J., Kopf M. CD40-CD40L cross-talk integrates strong antigenic signals and microbial stimuli to induce development of IL-17-producing CD4+ T cells. Proc Natl Acad Sci U S A 2009, 106:876-881.
24. Oelke K., Lu Q., Richardson D., Wu A., Deng C., Hanash S., et al. Overexpression of CD70 and overstimulation of IgG synthesis by lupus T cells and T cells treated with DNA methylation inhibitors. Arthritis Rheum 2004, 50:1850-1860.
25. Jiang H., Xiao R., Lian X., Kanekura T., Luo Y., Yin Y., et al. Demethylation of TNFSF7 contributes to CD70 overexpression in CD4+ T cells from patients with systemic sclerosis. Clin Immunol 2012, 143:39-44.
26. Yin H., Zhao M., Wu X., Gao F., Luo Y., Ma L., et al. Hypomethylation and overexpression of CD70 (TNFSF7) in CD4+ T cells of patients with primary Sjogren's syndrome. J Dermatol Sci 2010, 59:198-203.
27. Absher D.M., Li X., Waite L.L., Gibson A., Roberts K., Edberg J., et al. Genome-wide DNA methylation analysis of systemic lupus erythematosus reveals persistent hypomethylation of interferon genes and compositional changes to CD4+ T-cell populations. PLoS Genet 2013, 9:e1003678.
28. Altorok N., Coit P., Hughes T., Koelsch K.A., Stone D.U., Rasmussen A., et al. Genome-wide DNA methylation patterns in naive CD4+ T cells from patients with primary Sjogren's syndrome. Arthritis Rheumatol 2014, 66:731-739.
29. Coit P., Jeffries M., Altorok N., Dozmorov M.G., Koelsch K.A., Wren J.D., et al. Genome-wide DNA methylation study suggests epigenetic accessibility and transcriptional poising of interferon-regulated genes in naive CD4+ T cells from lupus patients. J Autoimmun 2013, 43:78-84.
30. Garaud S., Le Dantec C., Jousse-Joulin S., Hanrotel-Saliou C., Saraux A., Mageed R.A., et al. IL-6 modulates CD5 expression in B cells from patients with lupus by regulating DNA methylation. J Immunol 2009, 182:5623-5632.
31. Fali T., Le Dantec C., Thabet Y., Jousse S., Hanrotel C., Youinou P., et al. DNA methylation modulates HRES1/p28 expression in B cells from patients with Lupus. Autoimmunity 2014, 47:265-271.
32. Belkhir R., Gestermann N., Koutero M., Seror R., Tost J., Mariette X., et al. Upregulation of membrane-bound CD40L on CD4+ T cells in women with primary Sjogren's syndrome. Scand J Immunol 2014, 79:37-42.
33. Gestermann N., Koutero M., Belkhir R., Tost J., Mariette X., Miceli-Richard C. Methylation profile of the promoter region of IRF5 in primary Sjogren's syndrome. Eur Cytokine Netw 2012, 23:166-172.
34. Wang Y.Y., Wang Q., Sun X.H., Liu R.Z., Shu Y., Kanekura T., et al. DNA hypermethylation of the forkhead box protein 3 (FOXP3) promoter in CD4+ T cells of patients with systemic sclerosis. Br J Dermatol 2014, 171:39-47.
35. Li Y., Zhao M., Hou C., Liang G., Yang L., Tan Y., et al. Abnormal DNA methylation in CD4+ T cells from people with latent autoimmune diabetes in adults. Diabetes Res Clin Pract 2011, 94:242-248.
36. Janson P.C., Linton L.B., Bergman E.A., Marits P., Eberhardson M., Piehl F., et al. Profiling of CD4+ T cells with epigenetic immune lineage analysis. J Immunol 2011, 186:92-102.
37. Wang Y., Fan P.S., Kahaleh B. Association between enhanced type I collagen expression and epigenetic repression of the FLI1 gene in scleroderma fibroblasts. Arthritis Rheum 2006, 54:2271-2279.
38. Dees C., Schlottmann I., Funke R., Distler A., Palumbo-Zerr K., Zerr P., et al. The Wnt antagonists DKK1 and SFRP1 are downregulated by promoter hypermethylation in systemic sclerosis. Ann Rheum Dis 2014, 73:1232-1239.
39. Trenkmann M., Brock M., Gay R.E., Kolling C., Speich R., Michel B.A., et al. Expression and function of EZH2 in synovial fibroblasts: epigenetic repression of the Wnt inhibitor SFRP1 in rheumatoid arthritis. Ann Rheum Dis 2011, 70:1482-1488.
40. Nile C.J., Read R.C., Akil M., Duff G.W., Wilson A.G. Methylation status of a single CpG site in the IL6 promoter is related to IL6 messenger RNA levels and rheumatoid arthritis. Arthritis Rheum 2008, 58:2686-2693.
41. Takami N., Osawa K., Miura Y., Komai K., Taniguchi M., Shiraishi M., et al. Hypermethylated promoter region of DR3, the death receptor 3 gene, in rheumatoid arthritis synovial cells. Arthritis Rheum 2006, 54:779-787.
42. Baranzini S.E., Mudge J., van Velkinburgh J.C., Khankhanian P., Khrebtukova I., Miller N.A., et al. Genome, epigenome and RNA sequences of monozygotic twins discordant for multiple sclerosis. Nature 2010, 464:1351-1356.
43. Mastronardi F.G., Noor A., Wood D.D., Paton T., Moscarello M.A. Peptidyl argininedeiminase 2 CpG island in multiple sclerosis white matter is hypomethylated. J Neurosci Res 2007, 85:2006-2016.
44. Musse A.A., Boggs J.M., Harauz G. Deimination of membrane-bound myelin basic protein in multiple sclerosis exposes an immunodominant epitope. Proc Natl Acad Sci U S A 2006, 103:4422-4427.
45. Kouzarides T. Chromatin modifications and their function. Cell 2007, 128:693-705.
46. Hu N., Qiu X., Luo Y., Yuan J., Li Y., Lei W., et al. Abnormal histone modification patterns in lupus CD4+ T cells. J Rheumatol 2008, 35:804-810.
47. Zhou Y., Qiu X., Luo Y., Yuan J., Li Y., Zhong Q., et al. Histone modifications and methyl-CpG-binding domain protein levels at the TNFSF7 (CD70) promoter in SLE CD4+ T cells. Lupus 2011, 20:1365-1371.
48. Wang Y., Yang Y., Luo Y., Yin Y., Wang Q., Li Y., et al. Aberrant histone modification in peripheral blood B cells from patients with systemic sclerosis. Clin Immunol 2013, 149:46-54.
49. Pedre X., Mastronardi F., Bruck W., Lopez-Rodas G., Kuhlmann T., Casaccia P. Changed histone acetylation patterns in normal-appearing white matter and early multiple sclerosis lesions. J Neurosci 2011, 31:3435-3445.
50. Miao F., Chen Z., Zhang L., Liu Z., Wu X., Yuan Y.C., et al. Profiles of epigenetic histone post-translational modifications at type 1 diabetes susceptible genes. J Biol Chem 2012, 287:16335-16345.
51. Kramer M., Dees C., Huang J., Schlottmann I., Palumbo-Zerr K., Zerr P., et al. Inhibition of H3K27 histone trimethylation activates fibroblasts and induces fibrosis. Ann Rheum Dis 2013, 72:614-620.
52. Miao F., Smith D.D., Zhang L., Min A., Feng W., Natarajan R. Lymphocytes from patients with type 1 diabetes display a distinct profile of chromatin histone H3 lysine 9 dimethylation: an epigenetic study in diabetes. Diabetes 2008, 57:3189-3198.
53. Mattick J.S. Non-coding RNAs: the architects of eukaryotic complexity. EMBO Rep 2001, 2:986-991.
54. Chen C.Z., Schaffert S., Fragoso R., Loh C. Regulation of immune responses and tolerance: the microRNA perspective. Immunol Rev 2013, 253:112-128.
55. Pan W., Zhu S., Yuan M., Cui H., Wang L., Luo X., 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.
56. Wu X.N., Ye Y.X., Niu J.W., Li Y., Li X., You X., et al. Defective PTEN regulation contributes to B cell hyperresponsiveness in systemic lupus erythematosus. Sci Transl Med 2014, 6:246ra99.
57. Stagakis E., Bertsias G., Verginis P., Nakou M., Hatziapostolou M., Kritikos H., et al. Identification of novel microRNA signatures linked to human lupus disease activity and pathogenesis: miR-21 regulates aberrant T cell responses through regulation of PDCD4 expression. Ann Rheum Dis 2011, 70:1496-1506.
58. Zhu H., Luo H., Li Y., Zhou Y., Jiang Y., Chai J., et al. MicroRNA-21 in scleroderma fibrosis and its function in TGF-beta-regulated fibrosis-related genes expression. J Clin Immunol 2013, 33:1100-1109.
59. Murugaiyan G., Cunha A.P.d., Ajay A.K., Joller N., Garo L.P., Kumaradevan S., et al. MicroRNA-21 promotes Th17 differentiation and mediates experimental autoimmune encephalomyelitis. J Clin Invest 2015, 125:1069-1080.
60. Dong L., Wang X., Tan J., Li H., Qian W., Chen J., et al. Decreased expression of microRNA-21 correlates with the imbalance of Th17 and Treg cells in patients with rheumatoid arthritis. J Cell Mol Med 2014, 18:2213-2224.
61. Ruan Q., Wang T., Kameswaran V., Wei Q., Johnson D.S., Matschinsky F., et al. The microRNA-21-PDCD4 axis prevents type 1 diabetes by blocking pancreatic beta cell death. Proc Natl Acad Sci U S A 2011, 108:12030-12035.
62. Qin H., Zhu X., Liang J., Wu J., Yang Y., Wang S., et al. MicroRNA-29b contributes to DNA hypomethylation of CD4+ T cells in systemic lupus erythematosus by indirectly targeting DNA methyltransferase 1. J Dermatol Sci 2013, 69:61-67.
63. Smith K.M., Guerau-de-Arellano M., Costinean S., Williams J.L., Bottoni A., Mavrikis Cox G., et al. miR-29ab1 deficiency identifies a negative feedback loop controlling Th1 bias that is dysregulated in multiple sclerosis. J Immunol 2012, 189:1567-1576.
64. Maurer B., Stanczyk J., Jungel A., Akhmetshina A., Trenkmann M., Brock M., et al. MicroRNA-29, a key regulator of collagen expression in systemic sclerosis. Arthritis Rheum 2010, 62:1733-1743.
65. Carlsen A.L., Schetter A.J., Nielsen C.T., Lood C., Knudsen S., Voss A., et al. Circulating microRNA expression profiles associated with systemic lupus erythematosus. Arthritis Rheum 2013, 65:1324-1334.
66. Filkova M., Aradi B., Senolt L., Ospelt C., Vettori S., Mann H., et al. Association of circulating miR-223 and miR-16 with disease activity in patients with early rheumatoid arthritis. Ann Rheum Dis 2014, 73:1898-1904.
67. Ma X., Zhou J., Zhong Y., Jiang L., Mu P., Li Y., et al. Expression, regulation and function of microRNAs in multiple sclerosis. Int J Med Sci 2014, 11:810-818.
68. Heward J.A., Lindsay M.A. Long non-coding RNAs in the regulation of the immune response. Trends Immunol 2014, 35:408-419.
69. Wang P., Xue Y., Han Y., Lin L., Wu C., Xu S., et al. The STAT3-binding long noncoding RNA lnc-DC controls human dendritic cell differentiation. Science 2014, 344:310-313.
70. Carpenter S., Aiello D., Atianand M.K., Ricci E.P., Gandhi P., Hall L.L., et al. A long noncoding RNA mediates both activation and repression of immune response genes. Science 2013, 341:789-792.
71. Yuan J.H., Yang F., Wang F., Ma J.Z., Guo Y.J., Tao Q.F., et al. A long noncoding RNA activated by TGF-beta promotes the invasion-metastasis cascade in hepatocellular carcinoma. Cancer Cell 2014, 25:666-681.
72. Sharma S., Findlay G.M., Bandukwala H.S., Oberdoerffer S., Baust B., Li Z., et al. Dephosphorylation of the nuclear factor of activated T cells (NFAT) transcription factor is regulated by an RNA-protein scaffold complex. Proc Natl Acad Sci U S A 2011, 108:11381-11386.
73. Rapicavoli N.A., Qu K., Zhang J., Mikhail M., Laberge R.M., Chang H.Y. A mammalian pseudogene lncRNA at the interface of inflammation and anti-inflammatory therapeutics. Elife 2013, 2:e00762.
74. Modarresi F., Faghihi M.A., Lopez-Toledano M.A., Fatemi R.P., Magistri M., Brothers S.P., et al. Inhibition of natural antisense transcripts in vivo results in gene-specific transcriptional upregulation. Nat Biotechnol 2012, 30:453-459.
75. Carrieri C., Cimatti L., Biagioli M., Beugnet A., Zucchelli S., Fedele S., et al. Long non-coding antisense RNA controls Uchl1 translation through an embedded SINEB2 repeat. Nature 2012, 491:454-457.
76. Ulitsky I., Bartel D.P. lincRNAs: genomics, evolution, and mechanisms. Cell 2013, 154:26-46.
77. Huang B., Jiang C., Zhang R. Epigenetics: the language of the cell?. Epigenomics 2014, 6:73-88.
78. Hedrich C.M., Rauen T., Apostolidis S.A., Grammatikos A.P., Rodriguez Rodriguez N., Ioannidis C., et al. Stat3 promotes IL-10 expression in lupus T cells through trans-activation and chromatin remodeling. Proc Natl Acad Sci U S A 2014, 111:13457-13462.
79. Hemmatazad H., Rodrigues H.M., Maurer B., Brentano F., Pileckyte M., Distler J.H., et al. Histone deacetylase 7, a potential target for the antifibrotic treatment of systemic sclerosis. Arthritis Rheum 2009, 60:1519-1529.
80. Grabiec A.M., Korchynskyi O., Tak P.P., Reedquist K.A. Histone deacetylase inhibitors suppress rheumatoid arthritis fibroblast-like synoviocyte and macrophage IL-6 production by accelerating mRNA decay. Ann Rheum Dis 2012, 71:424-431.
81. Mishra N., Brown D.R., Olorenshaw I.M., Kammer G.M. Trichostatin A reverses skewed expression of CD154, interleukin-10, and interferon-gamma gene and protein expression in lupus T cells. Proc Natl Acad Sci U S A 2001, 98:2628-2633.
82. Patel T., Patel V., Singh R., Jayaraman S. Chromatin remodeling resets the immune system to protect against autoimmune diabetes in mice. Immunol Cell Biol 2011, 89:640-649.
83. Vojinovic J., Damjanov N., D'Urzo C., Furlan A., Susic G., Pasic S., et al. Safety and efficacy of an oral histone deacetylase inhibitor in systemic-onset juvenile idiopathic arthritis. Arthritis Rheum 2011, 63:1452-1458.
84. Chan M.W., Chang C.B., Tung C.H., Sun J., Suen J.L., Wu S.F. Low-dose 5-aza-2'-deoxycytidine pretreatment inhibits experimental autoimmune encephalomyelitis by induction of regulatory T cells. Mol Med 2014, 20:248-256.
85. Kroesen M., Gielen P., Brok I.C., Armandari I., Hoogerbrugge P.M., Adema G.J. HDAC inhibitors and immunotherapy; a double edged sword?. Oncotarget 2014, 5:6558-6572.
86. Tang Y., Luo X., Cui H., Ni X., Yuan M., Guo Y., et al. MicroRNA-146A contributes to abnormal activation of the type I interferon pathway in human lupus by targeting the key signaling proteins. Arthritis Rheum 2009, 60:1065-1075.
87. Ebert M.S., Neilson J.R., Sharp P.A. MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nat Methods 2007, 4:721-726.
88. Du C., Liu C., Kang J., Zhao G., Ye Z., Huang S., et al. MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis. Nat Immunol 2009, 10:1252-1259.
89. Gumireddy K., Young D.D., Xiong X., Hogenesch J.B., Huang Q., Deiters A. Small-molecule inhibitors of microRNA miR-21 function. Angew Chem Int Ed Engl 2008, 47:7482-7484.
90. Young D.D., Connelly C.M., Grohmann C., Deiters A. Small molecule modifiers of microRNA miR-122 function for the treatment of hepatitis C virus infection and hepatocellular carcinoma. J Am Chem Soc 2010, 132:7976-7981.
91. Li Y.T., Chen S.Y., Wang C.R., Liu M.F., Lin C.C., Jou I.M., et al. Brief report: amelioration of collagen-induced arthritis in mice by lentivirus-mediated silencing of microRNA-223. Arthritis Rheum 2012, 64:3240-3245.
92. Janssen H.L., Reesink H.W., Lawitz E.J., Zeuzem S., Rodriguez-Torres M., Patel K., et al. Treatment of HCV infection by targeting microRNA. N Engl J Med 2013, 368:1685-1694.
93. van der Ree M.H., van der Meer A.J., de Bruijne J., Maan R., van Vliet A., Welzel T.M., et al. Long-term safety and efficacy of microRNA-targeted therapy in chronic hepatitis C patients. Antiviral Res 2014, 111C:53-59.
94. Wang Z. The principles of MiRNA-masking antisense oligonucleotides technology. Methods Mol Biol 2011, 676:43-49.
95. Glossop J.R., Nixon N.B., Emes R.D., Haworth K.E., Packham J.C., Dawes P.T., et al. Epigenome-wide profiling identifies significant differences in DNA methylation between matched-pairs of T- and B-lymphocytes from healthy individuals. Epigenetics 2013, 8:1188-1197.
96. Graves M., Benton M., Lea R., Boyle M., Tajouri L., Macartney-Coxson D., et al. Methylation differences at the HLA-DRB1 locus in CD4+ T-cells are associated with multiple sclerosis. Mult Scler 2013, 20:1033-1041.
97. Zhao M., Tang J., Gao F., Wu X., Liang Y., Yin H., et al. Hypomethylation of IL10 and IL13 promoters in CD4+ T cells of patients with systemic lupus erythematosus. J Biomed Biotechnol 2010, 2010:931018.
98. Lu Q., Kaplan M., Ray D., Zacharek S., Gutsch D., Richardson B. Demethylation of ITGAL (CD11a) regulatory sequences in systemic lupus erythematosus. Arthritis Rheum 2002, 46:1282-1291.
99. Kaplan M.J., Lu Q., Wu A., Attwood J., Richardson B. Demethylation of promoter regulatory elements contributes to perforin overexpression in CD4+ lupus T cells. J Immunol 2004, 172:3652-3661.
100. Javierre B.M., Fernandez A.F., Richter J., Al-Shahrour F., Martin-Subero J.I., Rodriguez-Ubreva J., et al. Changes in the pattern of DNA methylation associate with twin discordance in systemic lupus erythematosus. Genome Res 2010, 20:170-179.
101. Kumagai C., Kalman B., Middleton F.A., Vyshkina T., Massa P.T. Increased promoter methylation of the immune regulatory gene SHP-1 in leukocytes of multiple sclerosis subjects. J Neuroimmunol 2012, 246:51-57.
102. Rakyan V.K., Beyan H., Down T.A., Hawa M.I., Maslau S., Aden D., et al. Identification of type 1 diabetes-associated DNA methylation variable positions that precede disease diagnosis. PLoS Genet 2011, 7:e1002300.
103. Miao C.G., Yang Y.Y., He X., Huang C., Huang Y., Qin D., et al. MicroRNA-152 modulates the canonical Wnt pathway activation by targeting DNA methyltransferase 1 in arthritic rat model. Biochimie 2014, 106:149-156.
104. Gonzalez S., Aguilera S., Alliende C., Urzua U., Quest A.F., Herrera L., et al. Alterations in type I hemidesmosome components suggestive of epigenetic control in the salivary glands of patients with Sjogren's syndrome. Arthritis Rheum 2011, 63:1106-1115.
105. Zhang Z., Song L., Maurer K., Petri M.A., Sullivan K.E. Global H4 acetylation analysis by ChIP-chip in systemic lupus erythematosus monocytes. Genes Immun 2010, 11:124-133.
106. Niederer F., Ospelt C., Brentano F., Hottiger M.O., Gay R.E., Gay S., et al. SIRT1 overexpression in the rheumatoid arthritis synovium contributes to proinflammatory cytokine production and apoptosis resistance. Ann Rheum Dis 2011, 70:1866-1873.
107. Makino K., Jinnin M., Hirano A., Yamane K., Eto M., Kusano T., et al. The downregulation of microRNA let-7a contributes to the excessive expression of type I collagen in systemic and localized scleroderma. J Immunol 2013, 190:3905-3915.
108. Chafin C.B., Regna N.L., Caudell D.L., Reilly C.M. MicroRNA-let-7a promotes E2F-mediated cell proliferation and NFkappaB activation in vitro. Cell Mol Immunol 2014, 11:79-83.
109. Roggli E., Gattesco S., Caille D., Briet C., Boitard C., Meda P., et al. Changes in microRNA expression contribute to pancreatic beta-cell dysfunction in prediabetic NOD mice. Diabetes 2012, 61:1742-1751.
110. Liu Y., Dong J., Mu R., Gao Y., Tan X., Li Y., et al. MicroRNA-30a promotes B cell hyperactivity in patients with systemic lupus erythematosus by direct interaction with Lyn. Arthritis Rheum 2013, 65:1603-1611.
111. Alsaleh G., Francois A., Philippe L., Gong Y.Z., Bahram S., Cetin S., et al. MiR-30a-3p negatively regulates BAFF synthesis in systemic sclerosis and rheumatoid arthritis fibroblasts. PLoS One 2014, 9:e111266.
112. Tanaka S., Suto A., Ikeda K., Sanayama Y., Nakagomi D., Iwamoto T., et al. Alteration of circulating miRNAs in SSc: miR-30b regulates the expression of PDGF receptor beta. Rheumatology (Oxford) 2013, 52:1963-1972.
113. Zhou Q., Haupt S., Kreuzer J.T., Hammitzsch A., Proft F., Neumann C., et al. Decreased expression of miR-146a and miR-155 contributes to an abnormal Treg phenotype in patients with rheumatoid arthritis. Ann Rheum Dis 2015, 74:1265-1274.
114. Pauley K.M., Stewart C.M., Gauna A.E., Dupre L.C., Kuklani R., Chan A.L., et al. Altered miR-146a expression in Sjogren's syndrome and its functional role in innate immunity. Eur J Immunol 2011, 41:2029-2039.
115. Moore C.S., Rao V.T., Durafourt B.A., Bedell B.J., Ludwin S.K., Bar-Or A., et al. miR-155 as a multiple sclerosis-relevant regulator of myeloid cell polarization. Ann Neurol 2013, 74:709-720.
116. Junker A., Krumbholz M., Eisele S., Mohan H., Augstein F., Bittner R., et al. MicroRNA profiling of multiple sclerosis lesions identifies modulators of the regulatory protein CD47. Brain 2009, 132:3342-3352.
117. Stanczyk J., Pedrioli D.M., Brentano F., Sanchez-Pernaute O., Kolling C., Gay R.E., et al. Altered expression of MicroRNA in synovial fibroblasts and synovial tissue in rheumatoid arthritis. Arthritis Rheum 2008, 58:1001-1009.
118. Gillespie J., Savic S., Wong C., Hempshall A., Inman M., Emery P., et al. Histone deacetylases are dysregulated in rheumatoid arthritis and a novel histone deacetylase 3-selective inhibitor reduces interleukin-6 production by peripheral blood mononuclear cells from rheumatoid arthritis patients. Arthritis Rheum 2012, 64:418-422.
119. Ge Z., Da Y., Xue Z., Zhang K., Zhuang H., Peng M., et al. Vorinostat, a histone deacetylase inhibitor, suppresses dendritic cell function and ameliorates experimental autoimmune encephalomyelitis. Exp Neurol 2013, 241:56-66.
120. Choo Q.Y., Ho P.C., Tanaka Y., Lin H.S. Histone deacetylase inhibitors MS-275 and SAHA induced growth arrest and suppressed lipopolysaccharide-stimulated NF-kappaB p65 nuclear accumulation in human rheumatoid arthritis synovial fibroblastic E11 cells. Rheumatology (Oxford) 2010, 49:1447-1460.
121. Saouaf S.J., Li B., Zhang G., Shen Y., Furuuchi N., Hancock W.W., et al. Deacetylase inhibition increases regulatory T cell function and decreases incidence and severity of collagen-induced arthritis. Exp Mol Pathol 2009, 87:99-104.
122. Lewis E.C., Blaabjerg L., Storling J., Ronn S.G., Mascagni P., Dinarello C.A., et al. The oral histone deacetylase inhibitor ITF2357 reduces cytokines and protects islet beta cells in vivo and in vitro. Mol Med 2011, 17:369-377.