Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, Second Xiangya Hospital, Central South University, #139 Renmin Middle Rd, Changsha, Hunan 410011, PR China.
J Autoimmun. 2013 Mar;41:1-5. doi: 10.1016/j.jaut.2013.01.010. Epub 2013 Feb 1.
Autoimmune diseases are characterized by aberrant immune responses against healthy cells and tissues, in which a given individual's genetic susceptibilities play a central role; however, the exact mechanisms underlying the development of these conditions remain for the most part unknown. In recent years, accumulating evidence has demonstrated that, in addition to genetics, other complementary mechanisms are involved in the pathogenesis of autoimmunity, in particular, epigenetics. Epigenetics is defined as stable and heritable patterns of gene expression that do not entail any alterations to the original DNA sequence. Epigenetic mechanisms primarily consist of DNA methylation, histone modifications and small non-coding RNA transcripts. Epigenetic marks can be affected by age and other environmental triggers, providing a plausible link between environmental factors and the onset and development of various human diseases. Because of their primary function in regulating timely gene expression, epigenetic mechanisms offer potential advantages in terms of interpreting the molecular basis of complicated diseases and providing new promising therapeutic avenues for their treatment. The present review focuses on recent progress made in elucidating the relationship between epigenetics and the pathogenesis of autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, primary Sjögren's syndrome, primary biliary cirrhosis, psoriasis and type 1 diabetes.
自身免疫性疾病的特征是针对健康细胞和组织的异常免疫反应,其中个体的遗传易感性起着核心作用;然而,这些疾病发展的确切机制在很大程度上仍然未知。近年来,越来越多的证据表明,除了遗传因素外,其他互补机制也参与了自身免疫的发病机制,特别是表观遗传学。表观遗传学被定义为基因表达的稳定且可遗传的模式,而不会导致原始 DNA 序列发生任何改变。表观遗传机制主要包括 DNA 甲基化、组蛋白修饰和小非编码 RNA 转录本。表观遗传标记可以受到年龄和其他环境触发因素的影响,为环境因素与各种人类疾病的发生和发展之间提供了合理的联系。由于其在调节适时基因表达方面的主要功能,表观遗传机制在解释复杂疾病的分子基础方面提供了潜在的优势,并为其治疗提供了新的有前途的治疗途径。本综述重点介绍了阐明表观遗传学与自身免疫性疾病发病机制之间关系的最新进展,包括系统性红斑狼疮、类风湿关节炎、系统性硬化症、原发性干燥综合征、原发性胆汁性肝硬化、银屑病和 1 型糖尿病。