Noori-Zadeh Ali, Mesbah-Namin Seyed Alireza, Saboor-Yaraghi Ali Akbar
Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
J Neurol Sci. 2017 Apr 15;375:203-208. doi: 10.1016/j.jns.2017.01.060. Epub 2017 Jan 24.
Multiple sclerosis (MS) is a chronic autoimmune disease with demyelination and neurodegeneration of the central nervous system. It has been shown that the regulatory T (Treg) cells are responsible for maintaining tolerance to self-antigens and can suppress the autoimmune process in several animal models such as experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Recent basic studies have demonstrated that forkhead box P (FOXP3) and BTB domain and CNC homolog 2 (BACH2) are the master transcription factors of these cells playing a pivotal role in the polarization of naïve T cells into Treg cells. In the current study, the expression of FOXP3 and BACH2 genes and FOXP3 promoter methylation were evaluated in T cells of the EAE-induced mice. The results of this study showed a prominent and significant hypermethylation of the FOXP3 gene promoter in the EAE-induced mice compared to the sham and control groups. The expression of FOXP3 and BACH2 genes was significantly decreased in the EAE group in comparison with the sham and control groups. This study suggests that the epigenetic modification of FOXP3 gene is involved in the pathogenesis of EAE and this could be important in therapy in an appropriate and logical statement.
多发性硬化症（MS）是一种慢性自身免疫性疾病，会导致中枢神经系统脱髓鞘和神经变性。研究表明，调节性T（Treg）细胞负责维持对自身抗原的耐受性，并能在多种动物模型中抑制自身免疫过程，如实验性自身免疫性脑脊髓炎（EAE），一种MS的小鼠模型。最近的基础研究表明，叉头框P（FOXP3）和BTB结构域及CNC同源物2（BACH2）是这些细胞的主要转录因子，在幼稚T细胞向Treg细胞的极化过程中起关键作用。在本研究中，评估了EAE诱导小鼠T细胞中FOXP3和BACH2基因的表达以及FOXP3启动子甲基化情况。本研究结果显示，与假手术组和对照组相比，EAE诱导小鼠中FOXP3基因启动子存在显著且明显的高甲基化。与假手术组和对照组相比，EAE组中FOXP3和BACH2基因的表达显著降低。本研究表明，FOXP3基因的表观遗传修饰参与了EAE的发病机制，这在以适当且合理的方式进行治疗方面可能具有重要意义。
