Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, People's Republic of China.
Department of Immunology, Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, No. 301 Xuefu Road, Zhenjiang, 212013, Jiangsu, People's Republic of China.
Clin Epigenetics. 2021 Nov 24;13(1):210. doi: 10.1186/s13148-021-01197-0.
The thymic microenvironment is mainly comprised of thymic epithelial cells, the cytokines, exosomes, surface molecules, and hormones from the cells, and plays a vital role in the development, differentiation, maturation and homeostasis of T lymphocytes. However, the thymus begins to degenerate as early as the second year of life and continues through aging in human beings, leading to a decreased output of naïve T cells, the limited TCR diversity and an expansion of monoclonal memory T cells in the periphery organs. These alternations will reduce the adaptive immune response to tumors and emerging infectious diseases, such as COVID-19, also it is easier to suffer from autoimmune diseases in older people. In the context of global aging, it is important to investigate and clarify the causes and mechanisms of thymus involution.
Epigenetics include histone modification, DNA methylation, non-coding RNA effects, and chromatin remodeling. In this review, we discuss how senescent thymic epithelial cells determine and control age-related thymic atrophy, how this process is altered by epigenetic modification. How the thymus adipose influences the dysfunctions of the thymic epithelial cells, and the prospects of targeting thymic epithelial cells for the treatment of thymus atrophy.
Epigenetic modifications are emerging as key regulators in governing the development and senescence of thymic epithelial cells. It is beneficial to re-establish effective thymopoiesis, identify the potential therapeutic strategy and rejuvenate the immune function in the elderly.
胸腺微环境主要由胸腺上皮细胞、细胞因子、外泌体、表面分子和激素组成，在 T 淋巴细胞的发育、分化、成熟和稳态中起着至关重要的作用。然而，胸腺早在生命的第二年就开始退化，并在人类衰老过程中持续退化，导致幼稚 T 细胞输出减少、TCR 多样性有限以及外周器官中单克隆记忆 T 细胞的扩增。这些改变将降低对肿瘤和新兴传染病（如 COVID-19）的适应性免疫反应，老年人也更容易患自身免疫性疾病。在全球老龄化的背景下，研究和阐明胸腺萎缩的原因和机制非常重要。
表观遗传学包括组蛋白修饰、DNA 甲基化、非编码 RNA 作用和染色质重塑。在这篇综述中，我们讨论了衰老的胸腺上皮细胞如何决定和控制与年龄相关的胸腺萎缩，以及这一过程如何被表观遗传修饰改变。胸腺脂肪如何影响胸腺上皮细胞的功能障碍，以及针对胸腺上皮细胞治疗胸腺萎缩的前景。
表观遗传修饰正在成为调节胸腺上皮细胞发育和衰老的关键调节因子。这有利于重新建立有效的胸腺生成，确定潜在的治疗策略，并恢复老年人的免疫功能。
