Department of Bio-medical Sciences, University of Catania, Via Androne, Catania (CT), Italy.
J Cell Physiol. 2014 Dec;229(12):1918-25. doi: 10.1002/jcp.24641.
Increasing evidence supports the role of epigenetics in the development of autoimmune disorders and the possibility of using epigenetic modifying drugs in the context of MS has not yet been investigated. We have explored the effect of the hypomethylating agent 5-aza-2'-deoxycytidine (DAC) in two murine models of experimental allergic encephalomyelitis (EAE). DAC treatment was associated with a significant amelioration of the clinical and histological hallmarks of EAE in both models. These effects were observed both in prophylactic and therapeutic regimens. The milder course of the disease was associated with a reduction in the number of spinal cord infiltrating lymphocytes and amelioration of the histopathological signs associated with EAE. In addition, increased transcript levels of anti-inflammatory cytokines and decreased mRNA expression of pro-inflammatory mediators were also observed. Finally, DAC treatment increased the percentage of circulating regulatory T cells by inducing Foxp3 expression via demethylation of a CpG island in Foxp3.
越来越多的证据支持表观遗传学在自身免疫性疾病发展中的作用，并且尚未研究在多发性硬化症的背景下使用表观遗传修饰药物的可能性。我们已经在两种实验性变应性脑脊髓炎（EAE）的小鼠模型中探索了去甲基化剂 5-氮杂-2'-脱氧胞苷（DAC）的作用。DAC 治疗与两种模型中 EAE 的临床和组织学特征的显著改善相关。这些作用在预防和治疗方案中均观察到。疾病的较轻病程与脊髓浸润淋巴细胞数量减少以及与 EAE 相关的组织病理学迹象的改善相关。此外，还观察到抗炎细胞因子的转录水平增加和促炎介质的 mRNA 表达减少。最后，DAC 通过去甲基化 Foxp3 中的 CpG 岛诱导 Foxp3 表达，从而增加循环调节性 T 细胞的百分比。
