Given its importance for T cell development and its decline with age, boosting thymic function represents a paradigm shifting approach for improving cancer therapies by stimulating endogenous T cell reactivity. Although the thymus is exquisitely sensitive to insult, such as that caused by stress, infection, or common cancer therapies, it also has a remarkable capacity for regeneration. Therefore, one approach to developing such immune boosting therapies is to understand and exploit the mechanisms that govern thymus repair. Our recent studies have identified two key pathways for thymic regeneration; centered on secretion of BMP4 by endothelial cells (ECs) and IL-23 by dendritic cells (DCs). However, the specific regulatory mechanisms that trigger these regeneration-associated factors after damage remain unclear. Given that (1) our prior work had revealed that the presence of CD4+CD8+ double positive (DP) thymocytes suppresses the production of regeneration factors; and (2) the high basal rate of thymocyte apoptosis; we hypothesized that apoptotic DP thymocytes were mediating this suppression. Consistent with this hypothesis, apoptotic thymocytes directly suppressed the production of BMP4 and IL-23 by ECs and DCs in vitro; and pan-caspase inhibition abrogated this effect. Consistent with this, inhibition of TAM receptors, which detect apoptotic cells and are expressed by ECs and DCs, enhanced the production of Il-23 and BMP4. Downstream of TAM receptor signaling, we found a complex interplay between activation of the RhoGTPase Rac1, sensing by the cytosolic pattern recognition receptor NOD2, and induction of miR29c; which led to the suppression of BMP4 and IL-23. Importantly disruption of this pathway with small molecule inhibitors to Rac1 led to robust production of BMP4 and IL-23 and enhanced thymic function in in vivo models of thymic damage. We therefore propose a model based on a “dead-man’s switch”, where apoptosis of thymocytes initiates tonic NOD2 signaling (via TAM receptors and Rac1) to suppress the production of regeneration factors; but depletion of thymocytes as a result of acute damage abrogates this pathway and unleashes the regenerative response. These findings not only reveal a novel molecular mechanism governing tissue regeneration, but also offer a superior therapeutic strategy for boosting thymic regeneration and T cell reconstitution after damage such as that caused by infection or cytoreductive therapy.