Angiolilli Chiara, Baeten Dominique L, Radstake Timothy R, Reedquist Kris A
Laboratory of Translational Immunology & Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
Amsterdam Rheumatology & Immunology Center, Department of Clinical Immunology & Rheumatology, Department of Experimental Immunology Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Epigenomics. 2017 Apr;9(4):447-461. doi: 10.2217/epi-2016-0136. Epub 2017 Jan 19.
Growing evidence supports the idea that aberrancies in epigenetic processes contribute to the onset and progression of human immune-mediated inflammatory diseases, such as rheumatoid arthritis (RA). Epigenetic regulators of histone tail modifications play a role in chromatin accessibility and transcriptional responses to inflammatory stimuli. Among these, histone deacetylases (HDACs) regulate the acetylation status of histones and nonhistone proteins, essential for immune responses. Broad-spectrum HDAC inhibitors are well-known anti-inflammatory agents and reduce disease severity in animal models of arthritis; however, selective HDAC inhibitors remain poorly studied. In this review, we describe emerging findings regarding the aberrant acetyl code in RA and other rheumatic disorders which may help identify not only novel diagnostic and prognostic clinical biomarkers for RA, but also new targets for epigenetic pharmacological applications.
越来越多的证据支持这样一种观点，即表观遗传过程中的异常变化会导致人类免疫介导的炎症性疾病（如类风湿关节炎，RA）的发生和发展。组蛋白尾部修饰的表观遗传调节因子在染色质可及性以及对炎症刺激的转录反应中发挥作用。其中，组蛋白去乙酰化酶（HDACs）调节组蛋白和非组蛋白的乙酰化状态，这对免疫反应至关重要。广谱HDAC抑制剂是众所周知的抗炎剂，可降低关节炎动物模型中的疾病严重程度；然而，选择性HDAC抑制剂的研究仍很少。在这篇综述中，我们描述了关于RA和其他风湿性疾病中异常乙酰化密码的新发现，这些发现不仅可能有助于识别RA新的诊断和预后临床生物标志物，还能为表观遗传药理学应用提供新靶点。
