DKK1 Mediated Inhibition of Wnt Signaling in Postnatal Mice Leads to Loss of TEC Progenitors and Thymic Degeneration

The study explored the importance of canonical Wnt signaling in the maintenance of thymic epithelial cells (TECs) in adult mice. By expressing the Wnt inhibitor DKK1 in TECs, researchers observed rapid thymic degeneration, characterized by a loss of TEC populations, decreased TEC proliferation, and the formation of cystic structures. The thymus was able to fully recover after the removal of DKK1, suggesting that Wnt signaling is crucial for the differentiation or proliferation of TECs necessary for maintaining the thymic microenvironment. The study also found that DKK1 expression led to a significant reduction in thymus size, particularly in male mice, and a decrease in total thymocyte numbers, without affecting thymocyte subset frequency. The loss of TECs, especially the K5K8DP TEC progenitors, resulted in thymic hypoplasia and altered morphology of cortical TECs. The study involved multiple experiments, with at least 3 animals per strain and sex, and a minimum of 50 areas counted in sections from multiple thymic lobes for each mean. The findings indicate that canonical Wnt signaling is essential for maintaining TEC progenitors and suggest that targeting this pathway could be beneficial for countering age-related thymic involution or thymic degeneration due to other causes. The number of mice used in the study was not specified in the provided text.