The multifaceted functional role of DNA methylation in immune-mediated rheumatic diseases

被引:0
|
作者
Matteo Vecellio
Haijing Wu
Qianjin Lu
Carlo Selmi
机构
[1] Humanitas Clinical and Research Center,Division of Rheumatology and Clinical Immunology
[2] IRCCS,Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences
[3] University of Oxford,BIOMETRA Department
[4] University of Milan,Hunan Key Laboratory of Medical Epigenomics, Department of Dermatology, The Second Xiangya Hospital
[5] Central South University,Department of Biomedical Sciences
[6] Humanitas University,undefined
来源
Clinical Rheumatology | 2021年 / 40卷
关键词
DNA methylation; Epigenetics; Rheumatic diseases;
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学科分类号
摘要
Genomic predisposition cannot explain the onset of complex diseases, as well illustrated by the largely incomplete concordance among monozygotic twins. Epigenetic mechanisms, including DNA methylation, chromatin remodelling and non-coding RNA, are considered to be the link between environmental stimuli and disease onset on a permissive genetic background in autoimmune and chronic inflammatory diseases. The paradigmatic cases of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Sjogren’s syndrome (SjS) and type-1 diabetes (T1D) share the loss of immunological tolerance to self-antigen influenced by several factors, with a largely incomplete role of individual genomic susceptibility. The most widely investigated epigenetic mechanism is DNA methylation which is associated with gene silencing and is due to the binding of methyl-CpG binding domain (MBD)-containing proteins, such as MECP2, to 5-methylcytosine (5mC). Indeed, a causal relationship occurs between DNA methylation and transcription factors occupancy and recruitment at specific genomic locus. In most cases, the results obtained in different studies are controversial in terms of DNA methylation comparison while fascinating evidence comes from the comparison of the epigenome in clinically discordant monozygotic twins. In this manuscript, we will review the mechanisms of epigenetics and DNA methylation changes in specific immune-mediated rheumatic diseases to highlight remaining unmet needs and to identify possible shared mechanisms beyond different tissue involvements with common therapeutic opportunities.Key Points• DNA methylation has a crucial role in regulating and tuning the immune system.• Evidences suggest that dysregulation of DNA methylation is pivotal in the context of immune-mediated rheumatic diseases.• DNA methylation dysregulation in FOXP3 and interferons-related genes is shared within several autoimmune diseases.• DNA methylation is an attractive marker for diagnosis and therapy.
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页码:459 / 476
页数:17
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