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;
D O I
暂无
中图分类号
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.
引用
收藏
页码:459 / 476
页数:17
相关论文
共 50 条
  • [1] The multifaceted functional role of DNA methylation in immune-mediated rheumatic diseases
    Vecellio, Matteo
    Wu, Haijing
    Lu, Qianjin
    Selmi, Carlo
    CLINICAL RHEUMATOLOGY, 2021, 40 (02) : 459 - 476
  • [2] Self or non-self? The multifaceted role of the microbiota in immune-mediated diseases
    Kriegel, Martin A.
    CLINICAL IMMUNOLOGY, 2015, 159 (02) : 119 - 121
  • [3] Sarcopenia, immune-mediated rheumatic diseases, and nutritional interventions
    Cruz-Jentoft, Alfonso J.
    Romero-Yuste, Susana
    Chamizo Carmona, Eugenio
    Nolla, Joan M.
    AGING CLINICAL AND EXPERIMENTAL RESEARCH, 2021, 33 (11) : 2929 - 2939
  • [4] Sarcopenia, immune-mediated rheumatic diseases, and nutritional interventions
    Alfonso J. Cruz-Jentoft
    Susana Romero-Yuste
    Eugenio Chamizo Carmona
    Joan M. Nolla
    Aging Clinical and Experimental Research, 2021, 33 : 2929 - 2939
  • [5] CHLORAMBUCIL IN THE TREATMENT OF PATIENTS WITH IMMUNE-MEDIATED RHEUMATIC DISEASES
    STEINBERG, AD
    ARTHRITIS AND RHEUMATISM, 1993, 36 (03): : 325 - 328
  • [6] Challenges in the Diagnosis of Chronic Immune-mediated Rheumatic Diseases
    Schirmer, Michael
    Duftner, Christina
    Dejaco, Christian
    DISCOVERY MEDICINE, 2013, 15 (82) : 160 - 165
  • [7] Sarcopenia in Immune-Mediated Rheumatic Diseases-Review
    Santo, Rafaela Cavalheiro do Espirito
    Baker, Joshua F.
    dos Santos, Leonardo Peterson
    da Silva, Mariana Marchezan Menezes
    Xavier, Ricardo Machado
    JCR-JOURNAL OF CLINICAL RHEUMATOLOGY, 2023, 29 (07) : 354 - 362
  • [8] Recent advances in cellular immunotherapy for immune-mediated rheumatic diseases
    Wan, Wei
    Liu, Yidi
    Gao, Jie
    Yan, Sijia
    Zhao, Dongbao
    INTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, 2025, 28 (01)
  • [9] Omics for the objective diagnosis and management of immune-mediated rheumatic diseases
    Fu, Tieh-Cheng
    Kung, Yen-Ying
    Lin, Jr-Rung
    Chang, Ching-Mao
    FRONTIERS IN MEDICINE, 2023, 10
  • [10] Main Oral Manifestations in Immune-Mediated and Inflammatory Rheumatic Diseases
    Gualtierotti, Roberta
    Marzano, Angelo Valerio
    Spadari, Francesco
    Cugno, Massimo
    JOURNAL OF CLINICAL MEDICINE, 2019, 8 (01)