Skip to main content
SpringerLink
Log in

Epigenetics in Non-tumor Immune-Mediated Skin Diseases

  • Review Article
  • Published:
Molecular Diagnosis & Therapy Aims and scope Submit manuscript

Abstract

Epigenetics is the study of the mechanisms that regulate gene expression without modifying DNA sequences. Knowledge of and evidence about how epigenetics plays a causative role in the pathogenesis of many skin diseases is increasing. Since the epigenetic changes present in tumor diseases have been thoroughly reviewed, we believe that knowledge of the new epigenetic findings in non-tumor immune-mediated dermatological diseases should be of interest to the general dermatologist. Hence, the purpose of this review is to summarize the recent literature on epigenetics in most non-tumor dermatological pathologies, focusing on psoriasis. Hyper- and hypomethylation of DNA methyltransferases and methyl-DNA binding domain proteins are the most common and studied methylation mechanisms. The acetylation and methylation of histones H3 and H4 are the most frequent and well-characterized histone modifications and may be associated with disease severity parameters and serve as therapeutic response markers. Many specific microRNAs dysregulated in non-tumor dermatological disease have been reviewed. Deepening the study of how epigenetic mechanisms influence non-tumor immune-mediated dermatological diseases might help us better understand the role of interactions between the environment and the genome in the physiopathogenesis of these diseases.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Waddington CH. The epigenotype. Int J Epidemiol. 2012;41:10–3. https://doi.org/10.1093/ije/dyr184.

    Article  CAS  PubMed  Google Scholar 

  2. Bird A. Perceptions of epigenetics. Nature. 2007;447:396–8. https://doi.org/10.1038/nature05913.

    Article  CAS  PubMed  Google Scholar 

  3. Portela A, Esteller M. Epigenetic modifications and human disease. Nat Biotechnol. 2010;28:1057–68. https://doi.org/10.1038/nbt.1685.

    Article  CAS  PubMed  Google Scholar 

  4. Aguilera O, Fernández AF, Muñoz A, et al. Epigenetics and environment: a complex relationship. J Appl Physiol. 2010;109:243–51. https://doi.org/10.1152/japplphysiol.00068.2010.

    Article  CAS  PubMed  Google Scholar 

  5. Zaidi SK, Young DW, Montecino M, et al. Bookmarking the genome: maintenance of epigenetic information. J Biol Chem. 2011;286:18355–61. https://doi.org/10.1074/jbc.R110.197061.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Rountree MR, Bachman KE, Herman JG, et al. DNA methylation, chromatin inheritance, and cancer. Oncogene. 2001;20:3156–65. https://doi.org/10.1038/sj.onc.1204339.

    Article  CAS  PubMed  Google Scholar 

  7. Hendrich B, Bird A. Identification and characterization of a family of mammalian methyl-CpG binding proteins. Mol Cell Biol. 1998;18:6538–47. https://doi.org/10.1128/mcb.18.11.6538.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Globisch D, Münzel M, Müller M, et al. Tissue distribution of 5-hydroxymethylcytosine and search for active demethylation intermediates, Croft AK, editor. PLoS One. 2010;5:e15367. https://doi.org/10.1371/journal.pone.0015367.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Wu H, D’Alessio AC, Ito S, et al. Genome-wide analysis of 5-hydroxymethylcytosine distribution reveals its dual function in transcriptional regulation in mouse embryonic stem cells. Genes Dev. 2011;25:679–84. https://doi.org/10.1101/gad.2036011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Tessarz P, Kouzarides T. Histone core modifications regulating nucleosome structure and dynamics. Nat Rev Mol Cell Biol. 2014;15:703–8. https://doi.org/10.1038/nrm3890.

    Article  CAS  PubMed  Google Scholar 

  11. Rando OJ. Combinatorial complexity in chromatin structure and function: revisiting the histone code. Curr Opin Genet Dev. 2012;22:148–55. https://doi.org/10.1016/j.gde.2012.02.013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Prakash K, Fournier D. Evidence for the implication of the histone code in building the genome structure. Biosystems. 2018;164:49–59. https://doi.org/10.1016/j.biosystems.2017.11.005.

    Article  CAS  PubMed  Google Scholar 

  13. Berger SL. Histone modifications in transcriptional regulation. Curr Opin Genet Dev. 2002;12:142–8. https://doi.org/10.1016/s0959-437x(02)00279-4.

    Article  CAS  PubMed  Google Scholar 

  14. Ernst J, Kellis M. Discovery and characterization of chromatin states for systematic annotation of the human genome. Nat Biotechnol. 2010;28:817–25. https://doi.org/10.1038/nbt.1662.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Rossetto D, Avvakumov N, Côté J. Histone phosphorylation: a chromatin modification involved in diverse nuclear events. Epigenetics. 2012;7:1098–108. https://doi.org/10.4161/epi.21975.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Bannister AJ, Kouzarides T. Regulation of chromatin by histone modifications. Cell Res. 2011;21:381–95. https://doi.org/10.1038/cr.2011.22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Swygert SG, Peterson CL. Chromatin dynamics: Interplay between remodeling enzymes and histone modifications. Biochim Biophys Acta BBA Gene Regul Mech. 2014;1839:728–36. https://doi.org/10.1016/j.bbagrm.2014.02.013.

    Article  CAS  Google Scholar 

  18. Bönisch C, Nieratschker SM, Orfanos NK, et al. Chromatin proteomics and epigenetic regulatory circuits. Expert Rev Proteomics. 2008;5:105–19. https://doi.org/10.1586/14789450.5.1.105.

    Article  PubMed  Google Scholar 

  19. Morera L, Lübbert M, Jung M. Targeting histone methyltransferases and demethylases in clinical trials for cancer therapy. Clin Epigenet. 2016;8:57. https://doi.org/10.1186/s13148-016-0223-4.

    Article  CAS  Google Scholar 

  20. Hyun K, Jeon J, Park K, et al. Writing, erasing and reading histone lysine methylations. Exp Mol Med. 2017;49:e324–e324. https://doi.org/10.1038/emm.2017.11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Audia JE, Campbell RM. Histone modifications and cancer. Cold Spring Harb Perspect Biol. 2016;8:a019521. https://doi.org/10.1101/cshperspect.a019521.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Zhang T, Cooper S, Brockdorff N. The interplay of histone modifications—writers that read. EMBO Rep. 2015;16:1467–81. https://doi.org/10.15252/embr.201540945.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Ravid T, Hochstrasser M. Diversity of degradation signals in the ubiquitin–proteasome system. Nat Rev Mol Cell Biol. 2008;9:679–89. https://doi.org/10.1038/nrm2468.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Weake VM, Workman JL. Histone ubiquitination: triggering gene activity. Mol Cell. 2008;29:653–63. https://doi.org/10.1016/j.molcel.2008.02.014.

    Article  CAS  PubMed  Google Scholar 

  25. Cao J, Yan Q. Histone ubiquitination and deubiquitination in transcription, DNA damage response, and cancer. Front Oncol [Internet]. 2012. https://doi.org/10.3389/fonc.2012.00026.

    Article  Google Scholar 

  26. Peschansky VJ, Wahlestedt C. Non-coding RNAs as direct and indirect modulators of epigenetic regulation. Epigenetics. 2014;9:3–12. https://doi.org/10.4161/epi.27473.

    Article  CAS  PubMed  Google Scholar 

  27. Liu Q, Wu D-H, et al. Roles of microRNAs in psoriasis: Immunological functions and potential biomarkers. Exp Dermatol. 2017;26:359–67. https://doi.org/10.1111/exd.13249.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Sonkoly E, Ståhle M, Pivarcsi A. MicroRNAs: novel regulators in skin inflammation. Clin Exp Dermatol. 2008;33:312–5. https://doi.org/10.1111/j.1365-2230.2008.02804.x.

    Article  CAS  PubMed  Google Scholar 

  29. Furer V, Greenberg JD, Attur M, et al. The role of microRNA in rheumatoid arthritis and other autoimmune diseases. Clin Immunol. 2010;136:1–15. https://doi.org/10.1016/j.clim.2010.02.005.

    Article  CAS  PubMed  Google Scholar 

  30. Deng X, Su Y, Wu H, et al. The role of microRNAs in autoimmune diseases with skin involvement. Scand J Immunol. 2015;81:153–65. https://doi.org/10.1111/sji.12261.

    Article  CAS  PubMed  Google Scholar 

  31. Coronnello C, Benos PV. ComiR: combinatorial microRNA target prediction tool. Nucleic Acids Res. 2013;41(W1):W159–64. https://doi.org/10.1093/nar/gkt379.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Quinn JJ, Chang HY. Unique features of long non-coding RNA biogenesis and function. Nat Rev Genet. 2016;17:47–62. https://doi.org/10.1038/nrg.2015.10.

    Article  CAS  PubMed  Google Scholar 

  33. Lodde V, Murgia G, Simula ER, et al. Long noncoding RNAs and circular RNAs in Autoimmune Diseases. Biomolecules. 2020;10:1044. https://doi.org/10.3390/biom10071044%3cc.

    Article  CAS  PubMed Central  Google Scholar 

  34. Dykes IM, Emanueli C. Transcriptional and post-transcriptional gene regulation by long non-coding RNA. Genom Proteom Bioinform. 2017;15:177–86. https://doi.org/10.1016/j.gpb.2016.12.005.

    Article  Google Scholar 

  35. Hur K, Kim S-H, Kim J-M. Potential implications of long noncoding RNAs in autoimmune diseases. Immune Netw. 2019;19(1):e4. https://doi.org/10.4110/in.2019.19.e4.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Meng S, Zhou H, Feng Z, et al. CircRNA: functions and properties of a novel potential biomarker for cancer. Mol Cancer. 2017;16:94. https://doi.org/10.1186/s12943-017-0663-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Zhou Z, Sun B, Huang S, et al. Roles of circular RNAs in immune regulation and autoimmune diseases. Cell Death Dis. 2019;10:503. https://doi.org/10.1038/s41419-019-1744-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Xia X, Tang X, Wang S. Roles of CircRNAs in autoimmune diseases. Front Immunol. 2019;10:639. https://doi.org/10.3389/fimmu.2019.00639.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Ebert MS, Sharp PA. MicroRNA sponges: progress and possibilities. RNA. 2010;16:2043–50. https://doi.org/10.1261/rna.2414110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Selmi C, Lu Q, Humble MC. Heritability versus the role of the environment in autoimmunity. J Autoimmun. 2012;39:249–52. https://doi.org/10.1016/j.jaut.2012.07.011.

    Article  PubMed  Google Scholar 

  41. Miller FW, Pollard KM, Parks CG, et al. Criteria for environmentally associated autoimmune diseases. J Autoimmun. 2012;39:253–8. https://doi.org/10.1016/j.jaut.2012.05.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Millington GW. Epigenetics and dermatological disease. Pharmacogenomics (diciembre de). 2008;9(12):1835–50. https://doi.org/10.2217/14622416.9.12.1835.

    Article  CAS  Google Scholar 

  43. 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 Investig. 1993;92:38–53. https://doi.org/10.1172/JCI116576.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Sahuquillo-Torralba A, de Unamuno-Bustos B. Impacto de la epigenética en el conocimiento de la patogenia y respuesta al tratamiento de la psoriasis. Piel. 2020;35:176–83. https://doi.org/10.1016/j.piel.2019.06.005.

    Article  Google Scholar 

  45. Boehncke W-H, Schön MP. Psoriasis. Lancet. 2015;386:983–94. https://doi.org/10.1016/S0140-6736(14)61909-7.

    Article  CAS  PubMed  Google Scholar 

  46. Nestle FO, Kaplan DH, Barker J. Psoriasis. N Engl J Med. 2009;361:496–509. https://doi.org/10.1056/NEJMra0804595.

    Article  CAS  PubMed  Google Scholar 

  47. Pollock RA, Abji F, Gladman DD. Epigenetics of psoriatic disease: a systematic review and critical appraisal. J Autoimmun. 2017;78:29–38. https://doi.org/10.1016/j.jaut.2016.12.002.

    Article  CAS  PubMed  Google Scholar 

  48. Trowbridge RM, Pittelkow MR. Epigenetics in the pathogenesis and pathophysiology of psoriasis vulgaris. J Drugs Dermatol JDD. 2014;13:111–8 (PMID: 24509958).

    CAS  PubMed  Google Scholar 

  49. Zhang P, Su Y, Lu Q. Epigenetics and psoriasis: epigenetics and psoriasis. J Eur Acad Dermatol Venereol. 2012;26:399–403. https://doi.org/10.1111/j.1468-3083.2011.04261.x.

    Article  CAS  PubMed  Google Scholar 

  50. Zhou F, Wang W, Shen C, et al. Epigenome-wide association analysis identified nine skin DNA methylation loci for psoriasis. J Investig Dermatol. 2016;136:779–87. https://doi.org/10.1016/j.jid.2015.12.029.

    Article  CAS  PubMed  Google Scholar 

  51. Chandra A, Senapati S, Roy S, et al. Epigenome-wide DNA methylation regulates cardinal pathological features of psoriasis. Clin Epigenet. 2018;10:108. https://doi.org/10.1186/s13148-018-0541-9.

    Article  CAS  Google Scholar 

  52. Zhang P, Su Y, Chen H, et al. Abnormal DNA methylation in skin lesions and PBMCs of patients with psoriasis vulgaris. J Dermatol Sci. 2010;60:40–2. https://doi.org/10.1016/j.jdermsci.2010.07.011.

    Article  CAS  PubMed  Google Scholar 

  53. Zhang P, Zhao M, Liang G, et al. Whole-genome DNA methylation in skin lesions from patients with psoriasis vulgaris. J Autoimmun. 2013;41:17–24. https://doi.org/10.1016/j.jaut.2013.01.001.

    Article  CAS  PubMed  Google Scholar 

  54. Roberson ED, Liu Y, Ryan C, et al. A subset of methylated CpG sites differentiate psoriatic from normal skin. J Investig Dermatol. 2012;132:583–92. https://doi.org/10.1038/jid.2011.348.

    Article  CAS  PubMed  Google Scholar 

  55. Hou R, Yin G, An P, et al. DNA methylation of dermal MSCs in psoriasis: identification of epigenetically dysregulated genes. J Dermatol Sci. 2013;72:103–9. https://doi.org/10.1016/j.jdermsci.2013.07.002.

    Article  CAS  PubMed  Google Scholar 

  56. Nobeyama Y, Umezawa Y, Nakagawa H. Less-invasive analysis of DNA methylation using psoriatic scales. J Dermatol Sci. 2016;83:70–3. https://doi.org/10.1016/j.jdermsci.2016.03.013.

    Article  CAS  PubMed  Google Scholar 

  57. Yooyongsatit S, Ruchusatsawat K, Noppakun N, et al. Patterns and functional roles of LINE-1 and Alu methylation in the keratinocyte from patients with psoriasis vulgaris. J Hum Genet. 2015;60:349–55. https://doi.org/10.1038/jhg.2015.33.

    Article  CAS  PubMed  Google Scholar 

  58. Gu X, Boldrup L, Coates PJ, et al. Epigenetic regulation of OAS2 shows disease-specific DNA methylation profiles at individual CpG sites. Sci Rep. 2016;6:32579. https://doi.org/10.1038/srep32579.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Ruchusatsawat K, Wongpiyabovorn J, Shuangshoti S, et al. SHP-1 promoter 2 methylation in normal epithelial tissues and demethylation in psoriasis. J Mol Med. 2006;84:175–82. https://doi.org/10.1007/s00109-005-0020-6.

    Article  CAS  PubMed  Google Scholar 

  60. Zhang K, Zhang R, Li X, et al. Promoter methylation status of p15 and p21 genes in HPP-CFCs of bone marrow of patients with psoriasis. Eur J Dermatol. 2009;19:141–6. https://doi.org/10.1684/ejd.2008.0618.

    Article  CAS  PubMed  Google Scholar 

  61. Zhang K, Zhang R, Li X, et al. The mRNA expression and promoter methylation status of the p16 gene in colony-forming cells with high proliferative potential in patients with psoriasis. Clin Exp Dermatol. 2007;32:702–8. https://doi.org/10.1111/j.1365-2230.2007.02458.x.

    Article  CAS  PubMed  Google Scholar 

  62. Chen M, Chen ZQ, Cui PG, et al. The methylation pattern of p16INK4a gene promoter in psoriatic epidermis and its clinical significance. Br J Dermatol. 2008;158:987–93. https://doi.org/10.1111/j.1365-2133.2008.08505.x.

    Article  CAS  PubMed  Google Scholar 

  63. Bai J, Liu Z, Xu Z, et al. Epigenetic downregulation of SFRP4 contributes to epidermal hyperplasia in psoriasis. J Immunol. 2015;194:4185–98. https://doi.org/10.4049/jimmunol.1403196.

    Article  CAS  PubMed  Google Scholar 

  64. Chen M, Wang Y, Yao X, et al. Hypermethylation of HLA-C may be an epigenetic marker in psoriasis. J Dermatol Sci. 2016;83:10–6.

    Article  CAS  PubMed  Google Scholar 

  65. Park GT, Han J, Park SG, et al. DNA methylation analysis of CD4+ T cells in patients with psoriasis. Arch Dermatol Res. 2014;306:259–68. https://doi.org/10.1007/s00403-013-1432-8.

    Article  CAS  PubMed  Google Scholar 

  66. Kim YI, Logan JW, Mason JB, et al. DNA hypomethylation in inflammatory arthritis: reversal with methotrexate. J Lab Clin Med. 1996;128:165–72. https://doi.org/10.1016/s0022-2143(96)90008-6.

    Article  CAS  PubMed  Google Scholar 

  67. Gu X, Nylander E, Coates PJ, et al. Correlation between reversal of DNA methylation and clinical symptoms in psoriatic epidermis following narrow-band UVB phototherapy. J Investig Dermatol. 2015;135:2077–83. https://doi.org/10.1038/jid.2015.128.

    Article  CAS  PubMed  Google Scholar 

  68. Zhang P, Su Y, Zhao M, et al. Abnormal histone modifications in PBMCs from patients with psoriasis vulgaris. Eur J Dermatol. 2011;21:552–627. https://doi.org/10.1684/ejd.2011.1383.

    Article  CAS  PubMed  Google Scholar 

  69. Ovejero-Benito MC, Reolid A, Sánchez-Jiménez P, et al. Histone modifications associated with biological drug response in moderate-to-severe psoriasis. Exp Dermatol. 2018;27:1361–71. https://doi.org/10.1111/exd.13790.

    Article  CAS  PubMed  Google Scholar 

  70. Clop A, Bertoni A, Spain SL, et al. An in-depth characterization of the major psoriasis susceptibility locus identifies candidate susceptibility alleles within an HLA-C enhancer element. Novelli G, editor. PLoS One. 2013;8(8):e71690. https://doi.org/10.1371/journal.pone.0071690.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Tovar-Castillo LE, Cancino-Díaz JC, García-Vázquez F, et al. Under-expression of VHL and over-expression of HDAC-1, HIF-1?, LL-37, and IAP-2 in affected skin biopsies of patients with psoriasis. Int J Dermatol. 2007;46:239–46. https://doi.org/10.1111/j.1365-4632.2006.02962.x.

    Article  CAS  PubMed  Google Scholar 

  72. Ekman AK, Enerbäck C. Lack of preclinical support for the efficacy of histone deacetylase inhibitors in the treatment of psoriasis. Br J Dermatol. 2016;174:424–6. https://doi.org/10.1111/bjd.14021.

    Article  CAS  PubMed  Google Scholar 

  73. McLaughlin F, Thangue N. Histone deacetylase inhibitors in psoriasis therapy. Curr Drug Target Inflamm Allergy. 2004;3:213–9. https://doi.org/10.2174/1568010043343859.

    Article  CAS  Google Scholar 

  74. Shuttleworth SJ, Bailey SG, Townsend PA. Histone deacetylase inhibitors: new promise in the treatment of immune and inflammatory diseases. Curr Drug Targets. 2010;11:1430–8. https://doi.org/10.2174/1389450111009011430.

    Article  CAS  PubMed  Google Scholar 

  75. Bovenschen HJ, van de Kerkhof PC, van Erp PE, et al. Foxp3+ regulatory T cells of psoriasis patients easily differentiate into IL-17A-producing cells and are found in lesional skin. J Investig Dermatol. 2011;131:1853–60. https://doi.org/10.1038/jid.2011.139.

    Article  CAS  PubMed  Google Scholar 

  76. Orecchia A, Scarponi C, Di Felice F, et al. Sirtinol treatment reduces inflammation in human dermal microvascular endothelial cells. PLoS One. 2011;6:e24307. https://doi.org/10.1371/journal.pone.0024307.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Hammitzsch A, de Wit J, Ridley A, et al. AB0022 comparison of in vitro effects of kinase and epigenetic inhibitors on TH17 responses in inflammatory arthritis. Ann Rheum Dis. 2014;73(Suppl 2):811.

    Article  Google Scholar 

  78. Hammitzsch A, Tallant C, Fedorov O, et al. CBP30, a selective CBP/p300 bromodomain inhibitor, suppresses human Th17 responses. Proc Natl Acad Sci. 2015;112:10768–73. https://doi.org/10.1073/pnas.1501956112.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Timis T, Orasan R. Understanding psoriasis: Role of miRNAs. Biomed Rep [Internet]. 2018. https://doi.org/10.3892/br.2018.1146.

    Article  Google Scholar 

  80. Sonkoly E. The expanding microRNA world in psoriasis. Exp Dermatol. 2017;26:375–6. https://doi.org/10.1111/exd.13275.

    Article  PubMed  Google Scholar 

  81. Wang MJ, Xu YY, Huang RY, et al. Role of an imbalanced miRNAs axis in pathogenesis of psoriasis: novel perspectives based on review of the literature. Oncotarget. 2017;8:5498–507. https://doi.org/10.18632/oncotarget.12534.

    Article  PubMed  Google Scholar 

  82. Hawkes JE, Nguyen GH, Fujita M, et al. microRNAs in psoriasis. J Investig Dermatol. 2016;136:365–71. https://doi.org/10.1038/JID.2015.409.

    Article  CAS  PubMed  Google Scholar 

  83. Wang Z, Jinnin M, Kudo H, et al. Detection of hair-microRNAs as the novel potent biomarker: evaluation of the usefulness for the diagnosis of scleroderma. J Dermatol Sci. 2013;72:134–41. https://doi.org/10.1016/j.jdermsci.2013.06.018.

    Article  CAS  PubMed  Google Scholar 

  84. Sonkoly E, Wei T, Pavez Loriè E, et al. Protein kinase C-dependent upregulation of miR-203 induces the differentiation of human keratinocytes. J Investig Dermatol (enero de). 2010;130(1):124–34. https://doi.org/10.1038/jid.2009.294.

    Article  CAS  Google Scholar 

  85. Sonkoly E, Wei T, Janson PCJ, et al. MicroRNAs: novel regulators involved in the pathogenesis of psoriasis? Zimmer J, editor. PLoS One. 2007;2:e610. https://doi.org/10.1371/journal.pone.0000610.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Xu N, Meisgen F, Butler LM, et al. MicroRNA-31 Is overexpressed in psoriasis and modulates inflammatory cytokine and chemokine production in keratinocytes via targeting serine/threonine kinase 40. J Immunol. 2013;190:678–88. https://doi.org/10.4049/jimmunol.1202695.

    Article  CAS  PubMed  Google Scholar 

  87. Yan S, Xu Z, Lou F, et al. NF-κB-induced microRNA-31 promotes epidermal hyperplasia by repressing protein phosphatase 6 in psoriasis. Nat Commun. 2015;6:7652. https://doi.org/10.1038/ncomms8652.

    Article  PubMed  Google Scholar 

  88. Lerman G, Avivi C, Mardoukh C, et al. MiRNA expression in psoriatic skin: reciprocal regulation of hsa-miR-99a and IGF-1R. Capogrossi MC, editor. PLoS One. 2011;6:e20916. https://doi.org/10.1371/journal.pone.0020916.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Sun D, Lee YS, Malhotra A, et al. miR-99 family of microRNAs suppresses the expression of prostate-specific antigen and prostate cancer cell proliferation. Cancer Res. 2011;71:1313–24. https://doi.org/10.1158/0008-5472.CAN-10-1031.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Xu N, Brodin P, Wei T, et al. MiR-125b, a microRNA downregulated in psoriasis, modulates keratinocyte proliferation by targeting FGFR2. J Investig Dermatol. 2011;131:1521–9. https://doi.org/10.1038/jid.2011.55.

    Article  CAS  PubMed  Google Scholar 

  91. Koga Y, Jinnin M, Ichihara A, et al. Analysis of expression pattern of serum microRNA levels in patients with psoriasis. J Dermatol Sci. 2014;74:170–1. https://doi.org/10.1016/j.jdermsci.2014.01.005.

    Article  CAS  PubMed  Google Scholar 

  92. Ichihara A, Jinnin M, Yamane K, et al. microRNA-mediated keratinocyte hyperproliferation in psoriasis vulgaris: microRNA-mediated keratinocyte hyperproliferation in psoriasis. Br J Dermatol. 2011;165:1003–10. https://doi.org/10.1111/j.1365-2133.2011.10497.x.

    Article  CAS  PubMed  Google Scholar 

  93. Tsuru Y, Jinnin M, Ichihara A, et al. miR-424 levels in hair shaft are increased in psoriatic patients. J Dermatol. 2014;41:382–5. https://doi.org/10.1111/1346-8138.12460.

    Article  CAS  PubMed  Google Scholar 

  94. Zhu H, Hou L, Liu J, et al. MiR-217 is down-regulated in psoriasis and promotes keratinocyte differentiation via targeting GRHL2. Biochem Biophys Res Commun. 2016;471:169–76. https://doi.org/10.1016/j.bbrc.2016.01.157.

    Article  CAS  PubMed  Google Scholar 

  95. Jiang M, Ma W, Gao Y, et al. IL-22-induced miR-122-5p promotes keratinocyte proliferation by targeting Sprouty2. Exp Dermatol. 2017;26:368–74. https://doi.org/10.1111/exd.13270.

    Article  CAS  PubMed  Google Scholar 

  96. Zibert JR, Løvendorf MB, Litman T, et al. MicroRNAs and potential target interactions in psoriasis. J Dermatol Sci. 2010;58:177–85. https://doi.org/10.1016/j.jdermsci.2010.03.004.

    Article  CAS  PubMed  Google Scholar 

  97. Meisgen F, Xu N, Wei T, et al. MiR-21 is up-regulated in psoriasis and suppresses T cell apoptosis: letter to the editor. Exp Dermatol. 2012;21:312–4. https://doi.org/10.1111/j.1600-0625.2012.01462.x.

    Article  CAS  PubMed  Google Scholar 

  98. Boele J, Persson H, Shin JW, et al. PAPD5-mediated 3’ adenylation and subsequent degradation of miR-21 is disrupted in proliferative disease. Proc Natl Acad Sci. 2014;111:11467–72. https://doi.org/10.1073/pnas.1317751111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Guinea-Viniegra J, Jimenez M, Schonthaler HB, et al. Targeting miR-21 to treat psoriasis. Sci Transl Med. 2014;6:225re1. https://doi.org/10.1126/scitranslmed.3008089.

    Article  CAS  PubMed  Google Scholar 

  100. Joyce CE, Zhou X, Xia J, et al. Deep sequencing of small RNAs from human skin reveals major alterations in the psoriasis miRNAome. Hum Mol Genet. 2011;20:4025–40. https://doi.org/10.1093/hmg/ddr331.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Roberts JC, Warren RB, Griffiths CEM, et al. Expression of microRNA-184 in keratinocytes represses argonaute 2: cytokine-induced miR-184 represses AGO2. J Cell Physiol. 2013;228:2314–23. https://doi.org/10.1002/jcp.24401.

    Article  CAS  PubMed  Google Scholar 

  102. Yu J, Ryan DG, Getsios S, et al. MicroRNA-184 antagonizes microRNA-205 to maintain SHIP2 levels in epithelia. Proc Natl Acad Sci. 2008;105:19300–5. https://doi.org/10.1073/pnas.0803992105.

    Article  PubMed  PubMed Central  Google Scholar 

  103. Fu D, Yu W, Li M, et al. MicroRNA-138 regulates the balance of Th1/Th2 via targeting RUNX3 in psoriasis. Immunol Lett. 2015;166:55–62. https://doi.org/10.1016/j.imlet.2015.05.014.

    Article  CAS  PubMed  Google Scholar 

  104. Wu R, Zeng J, Yuan J, et al. MicroRNA-210 overexpression promotes psoriasis-like inflammation by inducing Th1 and Th17 cell differentiation. J Clin Investig. 2018;128:2551–68. https://doi.org/10.1172/JCI97426.

    Article  PubMed  PubMed Central  Google Scholar 

  105. Zhao M, Wang L, Liang G, et al. Up-regulation of microRNA-210 induces immune dysfunction via targeting FOXP3 in CD4+ T cells of psoriasis vulgaris. Clin Immunol. 2014;150:22–30. https://doi.org/10.1016/j.clim.2013.10.009.

    Article  CAS  PubMed  Google Scholar 

  106. Hirao H, Jinnin M, Ichihara A, et al. Detection of hair root miR-19a as a novel diagnostic marker for psoriasis. Eur J Dermatol. 2013;23:807–11. https://doi.org/10.1684/ejd.2013.2190.

    Article  CAS  PubMed  Google Scholar 

  107. Oyama R, Jinnin M, Kakimoto A, et al. Circulating microRNA associated with TNF-α signaling pathway in patients with plaque psoriasis. J Dermatol Sci. 2011;61:209–11. https://doi.org/10.1016/j.jdermsci.2010.12.008.

    Article  CAS  PubMed  Google Scholar 

  108. Xia P, Fang X, Zhang Z, et al. Dysregulation of miRNA146a versus IRAK1 induces IL-17 persistence in the psoriatic skin lesions. Immunol Lett. 2012;148:151–62. https://doi.org/10.1016/j.imlet.2012.09.004.

    Article  CAS  PubMed  Google Scholar 

  109. Zhang W, Yi X, Guo S, et al. A single-nucleotide polymorphism of miR-146a and psoriasis: an association and functional study. J Cell Mol Med. 2014;18:2225–34. https://doi.org/10.1111/jcmm.12359.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Ichihara A, Jinnin M, Oyama R, et al. Increased serum levels of miR-1266 in patients with psoriasis vulgaris. Eur J Dermatol. 2012;22:68–71. https://doi.org/10.1684/ejd.2011.1600.

    Article  CAS  PubMed  Google Scholar 

  111. Guo S, Zhang W, Wei C, et al. Serum and skin levels of miR-369-3p in patients with psoriasis and their correlation with disease severity. Eur J Dermatol. 2013;23:608–13.

    Article  CAS  PubMed  Google Scholar 

  112. Løvendorf MB, Zibert JR, Gyldenløve M, et al. MicroRNA-223 and miR-143 are important systemic biomarkers for disease activity in psoriasis. J Dermatol Sci. 2014;75:133–9. https://doi.org/10.1016/j.jdermsci.2014.05.005.

    Article  CAS  PubMed  Google Scholar 

  113. Wang Z, Jinnin M, Harada M, et al. Diagnosis of nail psoriasis: evaluation of nail-derived microRNAs as potential novel biomarkers. Eur J Dermatol. 2017;27:20–7. https://doi.org/10.1684/ejd.2016.2906.

    Article  CAS  PubMed  Google Scholar 

  114. Liu R, Chang W, Li J, et al. Mesenchymal stem cells in psoriatic lesions affect the skin microenvironment through circular RNA. Exp Dermatol. 2019;28:292–9. https://doi.org/10.1111/exd.13890.

    Article  CAS  PubMed  Google Scholar 

  115. Liu R, Wang Q, Chang W, et al. Characterisation of the circular RNA landscape in mesenchymal stem cells from psoriatic skin lesions. Eur J Dermatol. 2019;29:29–38. https://doi.org/10.1684/ejd.2018.3483.

    Article  CAS  PubMed  Google Scholar 

  116. Qiao M, Ding J, Yan J, et al. Circular RNA expression profile and analysis of their potential function in psoriasis. Cell Physiol Biochem. 2018;50:15–27. https://doi.org/10.1159/000493952.

    Article  CAS  PubMed  Google Scholar 

  117. Ovejero-Benito MC, Cabaleiro T, Sanz-García A, et al. Epigenetic biomarkers associated with antitumour necrosis factor drug response in moderate-to-severe psoriasis. Br J Dermatol. 2018;178:798–800. https://doi.org/10.1111/bjd.15504.

    Article  CAS  PubMed  Google Scholar 

  118. Rosenberg A, Fan H, Chiu YG, et al. Divergent Gene Activation in Peripheral Blood and Tissues of Patients with Rheumatoid Arthritis, Psoriatic Arthritis and Psoriasis following Infliximab Therapy. Proost P, editor. PLoS One. 2014;9:e110657. https://doi.org/10.1371/journal.pone.0110657.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Mensà E, Recchioni R, Marcheselli F, et al. MiR-146a-5p correlates with clinical efficacy in patients with psoriasis treated with the tumour necrosis factor-alpha inhibitor adalimumab. Br J Dermatol. 2018;179:787–9. https://doi.org/10.1111/bjd.16659.

    Article  PubMed  Google Scholar 

  120. Lei W, Luo Y, Lei W, et al. Abnormal DNA methylation in CD4+ T cells from patients with systemic lupus erythematosus, systemic sclerosis, and dermatomyositis. Scand J Rheumatol. 2009;38:369–74. https://doi.org/10.1080/03009740902758875.

    Article  CAS  PubMed  Google Scholar 

  121. Balada E, Castro-Marrero J, Felip L, et al. Associations between the expression of epigenetically regulated genes and the expression of DNMTs and MBDs in systemic lupus erythematosus. Liossis S-N, editor. PLoS One. 2012;7:e45897. https://doi.org/10.1371/journal.pone.0045897.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Luo Y, Li Y, Su Y, et al. Abnormal DNA methylation in T cells from patients with subacute cutaneous lupus erythematosus. Br J Dermatol. 2008;159:827–33. https://doi.org/10.1111/j.1365-2133.2008.08758.x.

    Article  CAS  PubMed  Google Scholar 

  123. Ballestar E. Epigenetic alterations in autoimmune rheumatic diseases. Nat Rev Rheumatol. 2011;7:263–71. https://doi.org/10.1038/nrrheum.2011.16.

    Article  CAS  PubMed  Google Scholar 

  124. Hu N, Qiu X, Luo Y, et al. Abnormal histone modification patterns in lupus CD4+ T cells. J Rheumatol. 2008;35:804–10 (PMID: 18398941).

    CAS  PubMed  Google Scholar 

  125. Yin H, Wu H, Zhao M, et al. Histone demethylase JMJD3 regulates CD11a expression through changes in histone H3K27 tri-methylation levels in CD4+ T cells of patients with systemic lupus erythematosus. Oncotarget. 2017;8:48938–47. https://doi.org/10.18632/oncotarget.16894.

    Article  PubMed  PubMed Central  Google Scholar 

  126. Hedrich CM. Epigenetics in SLE. Curr Rheumatol Rep. 2017;19:58. https://doi.org/10.1007/s11926-017-0685-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Tang Y, Luo X, Cui H, 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;60:1065–75. https://doi.org/10.1002/art.24436.

    Article  CAS  PubMed  Google Scholar 

  128. Zhao X, Tang Y, Qu B, et al. MicroRNA-125a contributes to elevated inflammatory chemokine RANTES levels via targeting KLF13 in systemic lupus erythematosus. Arthritis Rheum. 2010;62:3425–35. https://doi.org/10.1002/art.27632.

    Article  CAS  PubMed  Google Scholar 

  129. 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;184:6773–81. https://doi.org/10.4049/jimmunol.0904060.

    Article  CAS  PubMed  Google Scholar 

  130. Duursma AM, Kedde M, Schrier M, et al. miR-148 targets human DNMT3b protein coding region. RNA. 2008;14:872–7. https://doi.org/10.1261/rna.972008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Divekar AA, Dubey S, Gangalum PR, et al. Dicer insufficiency and MicroRNA-155 overexpression in lupus regulatory T Cells: an apparent paradox in the setting of an inflammatory milieu. J Immunol. 2011;186:924–30. https://doi.org/10.4049/jimmunol.1002218.

    Article  CAS  PubMed  Google Scholar 

  132. Wen Z, Xu L, Chen X, et al. Autoantibody induction by DNA-containing immune complexes requires HMGB1 with the TLR2/MicroRNA-155 pathway. J Immunol. 2013;190:5411–22. https://doi.org/10.4049/jimmunol.1203301.

    Article  CAS  PubMed  Google Scholar 

  133. Lashine YA, Salah S, Aboelenein HR, et al. Correcting the expression of miRNA-155 represses PP2Ac and enhances the release of IL-2 in PBMCs of juvenile SLE patients. Lupus. 2015;24:240–7. https://doi.org/10.1177/0961203314552117.

    Article  CAS  PubMed  Google Scholar 

  134. Stagakis E, Bertsias G, Verginis P, 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;70:1496–506. https://doi.org/10.1136/ard.2010.139857.

    Article  CAS  PubMed  Google Scholar 

  135. 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. 2011;63:1376–86. https://doi.org/10.1002/art.30196.

    Article  CAS  PubMed  Google Scholar 

  136. Qin H, Zhu X, Liang J, 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;69:61–7. https://doi.org/10.1371/journal.pone.0217523.

    Article  CAS  PubMed  Google Scholar 

  137. Ding S, Liang Y, Zhao M, et al. Decreased microRNA-142-3p/5p expression causes CD4+ T cell activation and B cell hyperstimulation in systemic lupus erythematosus. Arthritis Rheum. 2012;64:2953–63. https://doi.org/10.1002/art.34505.

    Article  CAS  PubMed  Google Scholar 

  138. Zheng X, Zhang Y, Yue P, et al. Diagnostic significance of circulating miRNAs in systemic lupus erythematosus. Chokesuwattanaskul R, editor. PLoS One. 2019;14:e0217523. https://doi.org/10.1371/journal.pone.0217523.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Zhang F, Wu L, Qian J, et al. Identification of the long noncoding RNA NEAT1 as a novel inflammatory regulator acting through MAPK pathway in human lupus. J Autoimmun. 2016;75:96–104. https://doi.org/10.1016/j.jaut.2016.07.012.

    Article  CAS  PubMed  Google Scholar 

  140. Wang Y, Chen S, Chen S, et al. Long noncoding RNA expression profile and association with SLEDAI score in monocyte-derived dendritic cells from patients with systematic lupus erythematosus. Arthritis Res Ther. 2018;20:138. https://doi.org/10.1186/s13075-018-1640-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Xue Z, Cui C, Liao Z, et al. Identification of LncRNA Linc00513 containing lupus-associated genetic variants as a novel regulator of interferon signaling pathway. Front Immunol. 2018;9:2967. https://doi.org/10.3389/fimmu.2018.02967.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Wang Y, Fan P-S, Kahaleh B. Association between enhanced type I collagen expression and epigenetic repression of theFLI1 gene in scleroderma fibroblasts. Arthritis Rheum. 2006;54:2271–9. https://doi.org/10.1002/art.21948.

    Article  CAS  PubMed  Google Scholar 

  143. Luo Y, Wang Y, Wang Q, et al. Systemic sclerosis: Genetics and epigenetics. J Autoimmun. 2013;41:161–7. https://doi.org/10.1016/j.jaut.2013.01.012.

    Article  CAS  PubMed  Google Scholar 

  144. Hemmatazad H, Rodrigues HM, Maurer B, et al. Histone deacetylase 7, a potential target for the antifibrotic treatment of systemic sclerosis. Arthritis Rheum. 2009;60:1519–29. https://doi.org/10.1002/art.24494.

    Article  PubMed  Google Scholar 

  145. Miao C, Xiong Y, Yu H, et al. Critical roles of microRNAs in the pathogenesis of systemic sclerosis: new advances, challenges and potential directions. Int Immunopharmacol. 2015;28:626–33. https://doi.org/10.1016/j.intimp.2015.07.042.

    Article  CAS  PubMed  Google Scholar 

  146. Peng WJ, Tao JH, Mei B, et al. MicroRNA-29: a potential therapeutic target for systemic sclerosis. Expert Opin Ther Targets. 2012;16:875–9. https://doi.org/10.1517/14728222.2012.708339.

    Article  CAS  PubMed  Google Scholar 

  147. Sing T, Jinnin M, Yamane K, et al. microRNA-92a expression in the sera and dermal fibroblasts increases in patients with scleroderma. Rheumatology. 2012;51:1550–6. https://doi.org/10.1093/rheumatology/kes120.

    Article  CAS  PubMed  Google Scholar 

  148. Kajihara I, Jinnin M, Yamane K, et al. Increased accumulation of extracellular thrombospondin-2 due to low degradation activity stimulates type I collagen expression in scleroderma fibroblasts. Am J Pathol. 2012;180:703–14. https://doi.org/10.1016/j.ajpath.2011.10.030.

    Article  CAS  PubMed  Google Scholar 

  149. Zhu H, Li Y, Qu S, et al. MicroRNA expression abnormalities in limited cutaneous scleroderma and diffuse cutaneous scleroderma. J Clin Immunol. 2012;32:514–22. https://doi.org/10.1007/s10875-011-9647-y.

    Article  CAS  PubMed  Google Scholar 

  150. Zhu H, Luo H, Zuo X. MicroRNAs: their involvement in fibrosis pathogenesis and use as diagnostic biomarkers in scleroderma. Exp Mol Med. 2013;45:e41–e41. https://doi.org/10.1038/emm.2013.71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Honda N, Jinnin M, Kajihara I, et al. TGF-β-mediated downregulation of microRNA-196a contributes to the constitutive upregulated type I collagen expression in scleroderma dermal fibroblasts. J Immunol. 2012;188:3323–31. https://doi.org/10.4049/jimmunol.1100876.

    Article  CAS  PubMed  Google Scholar 

  152. Nakashima T, Jinnin M, Yamane K, et al. Impaired IL-17 signaling pathway contributes to the increased collagen expression in scleroderma fibroblasts. J Immunol. 2012;188:3573–83. https://doi.org/10.4049/jimmunol.1100591.

    Article  CAS  PubMed  Google Scholar 

  153. Honda N, Jinnin M, Kira-Etoh T, et al. miR-150 down-regulation contributes to the constitutive type I collagen overexpression in scleroderma dermal fibroblasts via the induction of integrin β3. Am J Pathol. 2013;182:206–16. https://doi.org/10.1016/j.ajpath.2012.09.023.

    Article  CAS  PubMed  Google Scholar 

  154. Makino K, Jinnin M, Kajihara I, et al. Circulating miR-142-3p levels in patients with systemic sclerosis: miR-142-3p levels in systemic sclerosis. Clin Exp Dermatol. 2012;37:34–9. https://doi.org/10.1016/j.ajpath.2012.09.023.

    Article  CAS  PubMed  Google Scholar 

  155. Inoue K, Jinnin M, Yamane K, et al. Down-regulation of miR-223 contributes to the formation of Gottron’s papules in dermatomyositis via the induction of PKCε. Eur J Dermatol. 2013;23:160–7. https://doi.org/10.1684/ejd.2013.1959.

    Article  CAS  PubMed  Google Scholar 

  156. Tang X, Tian X, Zhang Y, et al. Correlation between the frequency of Th17 Cell and the expression of microRNA-206 in patients with dermatomyositis. Clin Dev Immunol. 2013;2013:1–7. https://doi.org/10.1155/2013/345347.

    Article  CAS  Google Scholar 

  157. Shimada S, Jinnin M, Ogata A, et al. Serum miR-21 levels in patients with dermatomyositis. Clin Exp Rheumatol. 2013;31:161–2 (PMID: 23137528).

    PubMed  Google Scholar 

  158. Oshikawa Y, Jinnin M, Makino T, et al. Decreased miR-7 expression in the skin and sera of patients with dermatomyositis. Acta Derm Venereol. 2013;93:273–6. https://doi.org/10.2340/00015555-1459.

    Article  CAS  PubMed  Google Scholar 

  159. Kim E, Cook-Mills J, Morgan G, et al. Increased expression of vascular cell adhesion molecule 1 in muscle biopsy samples from juvenile dermatomyositis patients with short duration of untreated disease is regulated by miR-126. Arthritis Rheum. 2012;64:3809–17. https://doi.org/10.1002/art.34606.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Misunova M, Salinas-Riester G, Luthin S, et al. Microarray analysis of circulating micro RNAs in the serum of patients with polymyositis and dermatomyositis reveals a distinct disease expression profile and is associated with disease activity. Clin Exp Rheumatol. 2016;34:17–24 (PMID: 26574749).

    PubMed  Google Scholar 

  161. Gao S, Zhang H, Zuo X, et al. Integrated comparison of the miRNAome and mRNAome in muscles of dermatomyositis and polymyositis reveals common and specific miRNA–mRNAs. Epigenomics. 2019;11:23–33. https://doi.org/10.2217/epi-2018-0064.

    Article  CAS  PubMed  Google Scholar 

  162. Zhao M, Gao F, Wu X, et al. Abnormal DNA methylation in peripheral blood mononuclear cells from patients with vitiligo: abnormal DNA methylation in PBMCs of patients with vitiligo. Br J Dermatol. 2010;163:736–42. https://doi.org/10.1111/j.1365-2133.2010.09919.x.

    Article  CAS  PubMed  Google Scholar 

  163. Yan S, Shi J, Sun D, et al. Current insight into the roles of microRNA in vitiligo. Mol Biol Rep. 2020;47:3211–9. https://doi.org/10.1007/s11033-020-05336-3.

    Article  CAS  PubMed  Google Scholar 

  164. Mansuri MS, Singh M, Dwivedi M, et al. Micro RNA profiling reveals differentially expressed micro RNA signatures from the skin of patients with nonsegmental vitiligo. Br J Dermatol. 2014;171:1263–7. https://doi.org/10.1111/bjd.13109.

    Article  CAS  PubMed  Google Scholar 

  165. Wang Y, Wang K, Liang J, et al. Differential expression analysis of miRNA in peripheral blood mononuclear cells of patients with non-segmental vitiligo. J Dermatol. 2015;42:193–7. https://doi.org/10.1111/1346-8138.12725.

    Article  CAS  PubMed  Google Scholar 

  166. Shi YL, Weiland M, Li J, et al. MicroRNA expression profiling identifies potential serum biomarkers for non-segmental vitiligo. Pigment Cell Melanoma Res. 2013;26:418–21. https://doi.org/10.1111/pcmr.12086.

    Article  CAS  PubMed  Google Scholar 

  167. McDonagh AJG, Tazi-Ahnini R. Epidemiology and genetics of alopecia areata: epidemiology and genetics of alopecia areata. Clin Exp Dermatol. 2002;27:405–9. https://doi.org/10.1046/j.1365-2230.2002.01077.x.

    Article  CAS  PubMed  Google Scholar 

  168. McElwee KJ, Hoffmann R. Alopecia areata—animal models: alopecia areata in animal models. Clin Exp Dermatol. 2002;27:410–7. https://doi.org/10.1046/j.1365-2230.2002.01075.x.

    Article  CAS  PubMed  Google Scholar 

  169. Zhao M, Liang G, Wu X, et al. Abnormal epigenetic modifications in peripheral blood mononuclear cells from patients with alopecia areata: aberrant DNA methylation and histone modifications in AA. Br J Dermatol. 2012;166:266–73. https://doi.org/10.1111/j.1365-2133.2011.10646.x.

    Article  CAS  Google Scholar 

  170. Hessam S, Sand M, Lang K, et al. Altered Global 5-hydroxymethylation status in hidradenitis suppurativa: support for an epigenetic background. Dermatology. 2017;233:129–35. https://doi.org/10.1159/000478043.

    Article  CAS  PubMed  Google Scholar 

  171. Hessam S, Gambichler T, Skrygan M, Sand M, Rüddel I, Scholl L, et al. Reduced ten-eleven translocation and isocitrate dehydrogenase expression in inflammatory hidradenitis suppurativa lesions. Eur J Dermatol (julio de). 2018;28(4):449–56.

    Article  CAS  Google Scholar 

  172. Zhao M, Huang W, Zhang Q, et al. Aberrant epigenetic modifications in peripheral blood mononuclear cells from patients with pemphigus vulgaris: aberrant DNA methylation and histone modifications in PV. Br J Dermatol. 2012;167:523–31.

    Article  CAS  PubMed  Google Scholar 

  173. Wang M, Liang L, Li L, et al. Increased miR-424-5p expression in peripheral blood mononuclear cells from patients with pemphigus. Mol Med Rep. 2017;15:3479–84. https://doi.org/10.3892/mmr.2017.6422.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Lin N, Liu Q, Wang M, et al. Usefulness of miRNA-338-3p in the diagnosis of pemphigus and its correlation with disease severity. PeerJ. 2018;6:e5388. https://doi.org/10.7717/peerj.5388.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Xu M, Liu Q, Li S, et al. Increased expression of miR-338-3p impairs Treg-mediated immunosuppression in pemphigus vulgaris by targeting RUNX1. Exp Dermatol. 2020;29:623–9. https://doi.org/10.1111/exd.14111.

    Article  CAS  PubMed  Google Scholar 

  176. Liu Q, Cui F, Wang M, et al. Increased expression of microRNA-338-3p contributes to production of Dsg3 antibody in pemphigus vulgaris patients. Mol Med Rep [Internet]. 2018. https://doi.org/10.3892/mmr.2018.8934.

    Article  PubMed Central  Google Scholar 

  177. Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science. 2003;299:1057–61. https://doi.org/10.1126/science.1079490.

    Article  CAS  PubMed  Google Scholar 

  178. Bin L, Leung DYM. Genetic and epigenetic studies of atopic dermatitis. Allergy Asthma Clin Immunol. 2016;12:52. https://doi.org/10.1186/s13223-016-0158-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Liang Y, Chang C, Lu Q. The genetics and epigenetics of atopic dermatitis—filaggrin and other polymorphisms. Clin Rev Allergy Immunol. 2016;51:315–28. https://doi.org/10.1007/s12016-015-8508-5.

    Article  CAS  PubMed  Google Scholar 

  180. Rodríguez E, Baurecht H, Wahn AF, et al. An integrated epigenetic and transcriptomic analysis reveals distinct tissue-specific patterns of DNA methylation associated with atopic dermatitis. J Investig Dermatol. 2014;134:1873–83. https://doi.org/10.1038/jid.2014.87.

    Article  CAS  PubMed  Google Scholar 

  181. Ziyab AH, Karmaus W, Holloway JW, et al. DNA methylation of the filaggrin gene adds to the risk of eczema associated with loss-of-function variants: Filaggrin genetic and epigenetic influences on eczema. J Eur Acad Dermatol Venereol. 2013;27:e420–3. https://doi.org/10.1111/jdv.12000.

    Article  CAS  PubMed  Google Scholar 

  182. Tan HT, Ellis JA, Koplin JJ, et al. Methylation of the filaggrin gene promoter does not affect gene expression and allergy. Pediatr Allergy Immunol. 2014;25:608–10. https://doi.org/10.1111/pai.12245.

    Article  PubMed  Google Scholar 

  183. Luo Y, Zhou B, Zhao M, et al. Promoter demethylation contributes to TSLP overexpression in skin lesions of patients with atopic dermatitis. Clin Exp Dermatol. 2014;39:48–53. https://doi.org/10.1111/ced.12206.

    Article  CAS  PubMed  Google Scholar 

  184. Liang Y, Wang P, Zhao M, et al. Demethylation of the FCER1G promoter leads to FcεRI overexpression on monocytes of patients with atopic dermatitis: DNA methylation regulates AD monocyte FcεRI expression. Allergy. 2012;67:424–30. https://doi.org/10.1111/j.1398-9995.2011.02760.x.

    Article  CAS  PubMed  Google Scholar 

  185. Nakamura T, Sekigawa I, Ogasawara H, et al. Expression of DNMT-1 in patients with atopic dermatitis. Arch Dermatol Res. 2006;298:253–6. https://doi.org/10.1007/s00403-006-0682-0.

    Article  CAS  PubMed  Google Scholar 

  186. Sonkoly E, Janson P, Majuri ML, et al. MiR-155 is overexpressed in patients with atopic dermatitis and modulates T-cell proliferative responses by targeting cytotoxic T lymphocyte–associated antigen 4. J Allergy Clin Immunol. 2010;126(581–589):e20. https://doi.org/10.1016/j.jaci.2010.05.045.

    Article  CAS  Google Scholar 

  187. Quinn SR, Mangan NE, Caffrey BE, et al. The role of Ets2 transcription factor in the induction of microRNA-155 (miR-155) by lipopolysaccharide and its targeting by interleukin-10. J Biol Chem. 2014;289:4316–25. https://doi.org/10.1074/jbc.M113.522730.

    Article  CAS  PubMed  Google Scholar 

  188. Lv Y, Qi R, Xu J, et al. Profiling of serum and urinary microRNAs in children with atopic dermatitis. PLoS One. 2014;9(12):e115448. https://doi.org/10.1371/journal.pone.0115448.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Herberth G, Bauer M, Gasch M, et al. Maternal and cord blood miR-223 expression associates with prenatal tobacco smoke exposure and low regulatory T-cell numbers. J Allergy Clin Immunol. 2014;133(543–550):e4. https://doi.org/10.1016/j.jaci.2013.06.036.

    Article  CAS  Google Scholar 

  190. Hinz D, Bauer M, Röder S, et al. Cord blood Tregs with stable FOXP3 expression are influenced by prenatal environment and associated with atopic dermatitis at the age of 1 year. Allergy. 2012;67:380–9. https://doi.org/10.1111/j.1398-9995.2011.02767.x.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. M. C. Ovejero-Benito and E. Daudén contributed equally to the manuscript.

Authors and Affiliations

  1. Dermatology Department, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria La Princesa (IIS-IP), Diego de León, 62, 28006, Madrid, Spain

    Alejandra Reolid & E. Muñoz-Aceituno

  2. Clinical Pharmacology Department, Hospital Universitario de la Princesa, Instituto Teófilo Hernando, Universidad Autónoma de Madrid (UAM), Instituto de Investigación Sanitaria la Princesa (IIS-IP), Madrid, Spain

    F. Abad-Santos, M. C. Ovejero-Benito & E. Daudén

  3. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain

    F. Abad-Santos

Authors
  1. Alejandra Reolid
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. Muñoz-Aceituno
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F. Abad-Santos
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. C. Ovejero-Benito
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. E. Daudén
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alejandra Reolid.

Ethics declarations

Funding

No sources of funding were used to conduct this study or prepare this manuscript.

Conflict of interest

A. Reolid, E. Muñoz-Aceituno, F. Abad-Santos, MC. Ovejero-Benito, and E. Daudén have no conflicts of interest that are directly relevant to the content of this article.

Ethics approval

Not applicable.

Consent

Not applicable.

Author contributions

A. Reolid contributed to the design and implementation of the research, to the analysis of the results, and to the writing of the manuscript. MC. Ovejero-Benito and E. Daudén participated in drafting the article or revising it critically for important intellectual content. E. Muñoz-Aceituno and F. Abad-Santos gave final approval of the version to be submitted and any revised versions.

Data availability statement

Not applicable.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Reolid, A., Muñoz-Aceituno, E., Abad-Santos, F. et al. Epigenetics in Non-tumor Immune-Mediated Skin Diseases. Mol Diagn Ther 25, 137–161 (2021). https://doi.org/10.1007/s40291-020-00507-1

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40291-020-00507-1

Search

Navigation