Epigenetic modifications in thymic epithelial cells: an evolutionary perspective for thymus atrophy

Abstract

Background 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. Main body 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. Conclusion 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.

The effect of modified Qiyuan paste on mice with low immunity and sleep deprivation by regulating GABA nerve and immune system

“…Being the major lymphoid organ, the thymus is a pertinent site for the development, differentiation, and maturation of T lymphocytes [ 89 ]. The spleen is the largest secondary lymphoid organ in the body, where several T and B lymphocytes settle down and participate in various immune functions [ 90 , 91 ]. Wu [ 92 ] et al documented that traditional Chinese medicine increased the activities of acid phosphatase (ACP) and lactate dehydrogenase (LDH) in the spleen of immunocompromised mice.…”

Comprehensive Transcriptomic Analysis for Thymic Epithelial Cells of Aged Mice and Humans

“…Furthermore, our investigation revealed significant epigenetic changes in both mouse and human TECs during aging, which can impact various aspects of TEC function and senescence. Previous studies have demonstrated the influence of epigenetic changes on the expression of Foxn1, the epithelial-to-mesenchymal transition of TECs to adipocytes, and the expression of tissue-restricted self-Ags ( 39 40 ). Moreover, our analysis also highlighted potential involvement of other unstudied epigenetic factors, such as histone methylation, histone acetylation, and DNA methylation, which may contribute to age-related TEC dysfunction.…”

Thymus in Cardiometabolic Impairments and Atherosclerosis: Not a Silent Player?

“…Acute thymic involution may also take place. It is induced by different microbes, glucocorticoids, radiation, or use of chemotherapy and is associated with development of inflammation [21]. It has been demonstrated that premature thymus atrophy is at least partially caused by the damage of stromal cells by oxidative stress, associated with the deficiency of catalase, an important enzyme-antioxidant catalyzing reaction in which hydrogen peroxide turns into water and oxygen [22].…”

“…Neither of them can be rejected, just as neither can be accepted without hesitation. First is that cells of the perivascular space, such as mesenchymal stem cells, perivascular cells, and pericytes, differentiate into adipocytes through the activation of peroxisome proliferator-activated receptors (PPARγ), the main adipogenic transcription factor [21].…”