Figure 1.

Therapeutic approaches for boosting thymus function. Regenerative therapies to boost thymic function after acute damage or to reverse age-related involution can be broadly stratified into four subgroups based on their cellular or molecular targets: (1) targeting the epithelial microenvironment that supports thymopoiesis; (2) targeting the precursors that provide the supply of developing thymocytes; (3) modulation of hormones and metabolism; and (4) cellular therapies and bioengineering. However, within each of these therapeutic modalities there are key nexus points at which they act mechanistically. One approach relies on stimulating TEC function, such as IL-22, BMP4, KGF, RANKL, SSI, which act by either promoting survival, proliferation, differentiation, or expression of key thymopoietic molecules like DLL4 and KITL. In contrast, approaches such as administration of exogenous IL-7 and chemokine therapies target T cell precursors to promote their migration, proliferation, and differentiation directly. Similarly, many of the bioengineering approaches have sought to recapitulate these same functions such as providing TEC signals or a ready supply of T cell precursors. Elements of the figure were generated using Biorender.com.