Figure 1.

Aging-related changes of Treg generation and homeostasis. During aging there is a decreased generation of tTregs and pTregs. Thymic involution and reduced input of progenitor cells from the bone marrow result in a reduced output of recent thymic emigrants, among which are also less tTregs. In addition, in the peripheral tissues, for instance in the gut, there is a reduced induction of pTregs from naïve CD4⁺ T cells, likely due to age-associated changes in bacterial-derived metabolites, e.g. short chain fatty acids (SCFAs), or DC-derived Treg-inducing molecules, e.g. TGF-β or retinoic acid. Nevertheless, during aging there is an accumulation of Tregs in SLOs. This is mainly attritubed to the enhanced ability of old Tregs to escape apoptosis by selectively downregulating the expression of the pro-apoptotic protein Bim via the IL-6-ICOS-Bim axis. In addition, owing to the decreased production of naïve Tregs from the thymus, there is a resulting increase of effector Tregs in the elderly.