Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, California, USA.
Department of Medicine, Palo Alto Veterans Administration Healthcare System, Palo Alto, California, USA.
J Leukoc Biol. 2018 Oct;104(4):691-699. doi: 10.1002/JLB.1RI0418-160R. Epub 2018 Jun 27.
T cells are a heterogeneous population of cells that differ in their differentiation stages. Functional states are reflected in the epigenome that confers stability in cellular identity and is therefore important for naïve as well as memory T cell function. In many cellular systems, changes in chromatin structure due to alterations in histone expression, histone modifications and DNA methylation are characteristic of the aging process and cause or at least contribute to cellular dysfunction in senescence. Here, we review the epigenetic changes in T cells that occur with age and discuss them in the context of canonical epigenetic marks in aging model systems as well as recent findings of chromatin accessibility changes in T cell differentiation. Remarkably, transcription factor networks driving T cell differentiation account for many of the age-associated modifications in chromatin structures suggesting that loss of quiescence and activation of differentiation pathways are major components of T cell aging.
T 细胞是一群异质性的细胞,它们在分化阶段有所不同。功能状态反映在赋予细胞身份稳定性的表观基因组中,因此对于幼稚 T 细胞和记忆 T 细胞的功能都很重要。在许多细胞系统中,由于组蛋白表达、组蛋白修饰和 DNA 甲基化的改变而导致的染色质结构的变化是衰老过程的特征,并导致或至少有助于衰老过程中的细胞功能障碍。在这里,我们回顾了随着年龄的增长 T 细胞中发生的表观遗传变化,并在衰老模型系统中的经典表观遗传标记以及 T 细胞分化中染色质可及性变化的最新发现的背景下对其进行了讨论。值得注意的是,驱动 T 细胞分化的转录因子网络解释了许多与年龄相关的染色质结构修饰,这表明静止状态的丧失和分化途径的激活是 T 细胞衰老的主要组成部分。