Molecular control over thymic involution: From cytokines and microRNA to aging and adipose tissue

Abstract

The thymus is the primary organ for T-cell differentiation and maturation. Unlike other major organs, the thymus is highly dynamic, capable of undergoing multiple rounds of almost complete atrophy followed by rapid restoration. The process of thymic atrophy, or involution, results in decreased thymopoiesis and emigration of naïve T cells to the periphery. Multiple processes can trigger transient thymic involution, including bacterial and viral infection(s), aging, pregnancy and stress. Intense investigations into the mechanisms that underlie thymic involution have revealed diverse cellular and molecular mediators, with elaborate control mechanisms. This review outlines the disparate pathways through which involution can be mediated, from the transient infection-mediated pathway, tightly controlled by microRNA, to the chronic changes that occur through aging.

Characterization and Angiogenic Potential of Human Neonatal and Infant Thymus Mesenchymal Stromal Cells

“…The thymus gland involutes after infection, injury, and chemotherapy [57]. Resolution of thymic stress initiates a potent regenerative response in the thymus gland.…”

Differential effects of γc cytokines on postselection differentiation of CD8 thymocytes

“…47 The results of the present study therefore suggest that injection of rIL-21 alone or with rIL-7 might represent a promising and unforeseen strategy to enhance thymic function in subjects with age-or disease-related thymic atrophy. [48][49][50] …”

Thymic Mesenchymal Cells Have a Distinct Transcriptomic Profile

“…The latter four genes have anti-inflammatory effects either directly (Tgfb1) (52), or by enhancing efferocytosis (Cfh) (53), scavenging extracellular free radicals (Cp) (54), or mediating the disposal of extracellular misfolded proteins (Clu) (55). Relevance of inflammation resolution in the thymus and bone is linked to the fact that chronic inflammation accelerates ageing of the thymus and HSCs (56)(57)(58).…”