Division of Rheumatology, Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Antioxid Redox Signal. 2022 Mar;36(7-9):423-440. doi: 10.1089/ars.2021.0066. Epub 2022 Jan 4.
Epigenetic dysregulation plays an important role in the pathogenesis and development of autoimmune diseases. Oxidative stress is associated with autoimmunity and is also known to alter epigenetic mechanisms. Understanding the interplay between oxidative stress and epigenetics will provide insights into the role of environmental triggers in the development of autoimmunity in genetically susceptible individuals. Abnormal DNA and histone methylation patterns in genes and pathways involved in interferon and tumor necrosis factor signaling, cellular survival, proliferation, metabolism, organ development, and autoantibody production have been described in autoimmunity. Inhibitors of DNA and histone methyltransferases showed potential therapeutic effects in animal models of autoimmune diseases. Oxidative stress can regulate epigenetic mechanisms effects on DNA damage repair mechanisms, cellular metabolism and the local redox environment, and redox-sensitive transcription factors and pathways. Studies looking into oxidative stress and epigenetics in autoimmunity are relatively limited. The number of available longitudinal studies to explore the role of DNA methylation in the development of autoimmune diseases is small. Exploring the relationship between oxidative stress and epigenetics in autoimmunity will provide clues for potential preventative measures and treatment strategies. Inception cohorts with longitudinal follow-up would help to evaluate epigenetic marks as potential biomarkers for disease development, progression, and treatment response in autoimmunity. . 36, 423-440.
表观遗传失调在自身免疫性疾病的发病机制和发展中起着重要作用。氧化应激与自身免疫有关，并且已知其可改变表观遗传机制。了解氧化应激与表观遗传之间的相互作用将深入了解环境触发因素在遗传易感个体自身免疫发展中的作用。在自身免疫中，已描述了干扰素和肿瘤坏死因子信号转导、细胞存活、增殖、代谢、器官发育和自身抗体产生中涉及的基因和途径的异常 DNA 和组蛋白甲基化模式。DNA 和组蛋白甲基转移酶抑制剂在自身免疫性疾病的动物模型中显示出潜在的治疗效果。氧化应激可以调节表观遗传机制——对 DNA 损伤修复机制、细胞代谢和局部氧化还原环境以及氧化还原敏感转录因子和途径的影响。研究自身免疫中的氧化应激和表观遗传学相对有限。探讨 DNA 甲基化在自身免疫性疾病发展中作用的可用纵向研究数量较少。探索自身免疫中的氧化应激和表观遗传学之间的关系将为潜在的预防措施和治疗策略提供线索。具有纵向随访的起始队列将有助于评估表观遗传标记作为自身免疫性疾病发展、进展和治疗反应的潜在生物标志物。
