Department of Medical Immunology, Medical University of Gdansk, 80-210 Gdańsk, Poland.
Int J Mol Sci. 2021 Jul 1;22(13):7144. doi: 10.3390/ijms22137144.
Regulatory T cells (Tregs) exert a highly suppressive function in the immune system. Disturbances in their function predispose an individual to autoimmune dysregulation, with a predominance of the pro-inflammatory environment. Besides , which is a master regulator of these cells, other genes (e.g., and ) are also involved in Tregs development and function. Multidimensional Tregs suppression is determined by factors that are believed to be crucial in the action of Tregs-related genes. Among them, epigenetic changes, such as DNA methylation, tend to be widely studied over the past few years. DNA methylation acts as a repressive mark, leading to diminished gene expression. Given the role of increased CpG methylation upon Tregs imprinting and functional stability, alterations in the methylation pattern can cause an imbalance in the immune response. Due to the fact that epigenetic changes can be reversible, so-called epigenetic modifiers are broadly used in order to improve Tregs performance. In this review, we place emphasis on the role of DNA methylation of the genes that are key regulators of Tregs function. We also discuss disease settings that have an impact on the methylation status of Tregs and systematize the usefulness of epigenetic drugs as factors able to influence Tregs functions.
调节性 T 细胞(Tregs)在免疫系统中发挥着高度抑制功能。其功能障碍使个体易患自身免疫失调,促炎环境占主导地位。此外,Foxp3 是这些细胞的主要调节因子,其他基因(如 CTLA-4 和 IL-2RA)也参与 Tregs 的发育和功能。Tregs 的多维抑制是由被认为在 Tregs 相关基因作用中至关重要的因素决定的。其中,表观遗传变化,如 DNA 甲基化,近年来受到广泛研究。DNA 甲基化作为一种抑制标记,导致基因表达减少。鉴于 Tregs 印迹和功能稳定性中 CpG 甲基化增加的作用,甲基化模式的改变可能导致免疫反应失衡。由于表观遗传变化是可逆的,因此广泛使用所谓的表观遗传修饰剂来改善 Tregs 的性能。在这篇综述中,我们重点介绍了调节 Tregs 功能的关键基因的 DNA 甲基化作用。我们还讨论了影响 Tregs 甲基化状态的疾病情况,并将表观遗传药物的有用性系统化为能够影响 Tregs 功能的因素。