Extrinsic factors significantly influence thymus development in fetal thymus-kidney transplantation 2847

Abstract Description The “time-clock” regulates thymus development and growth. While the intrinsic clock hypothesis suggests thymic development is primarily driven by internal mechanisms, external factors may also influence growth. To investigate the thymus-intrinsic “clock” and its interaction with extrinsic cues, we transplanted fetal thymi at E13.5 and E15.5 under the kidney capsule. We hypothesized that if thymic tissues follow distinct developmental timelines based on their initial stages and stop at the same size, it would support an intrinsic mechanism. Alternatively, if growth rates and involution timing converge while maintaining different sizes, it would indicate a stronger role for extrinsic factors. Our data show that E13.5 and E15.5 thymic tissues exhibited gradual size and total cell count increases, with E15.5 tissues consistently larger. Both groups followed similar growth patterns, peaking at day 28, stabilizing until day 42, and subsequently declining. CD4/CD8, DN1a/b αβT, γδT, thymic NK, and B cell subsets displayed distinct proportions at earlier time points but converged by day 42. These findings suggest extrinsic cues significantly influence thymic development in Fetal Thymus-Kidney Transplantation. Transplanting fetal thymi into the kidney capsule provides a robust model to investigate intrinsic clocks and extrinsic signals in thymic development and aging. Funding Sources This work was supported by the National Institute of Health (grant number: P01 AG052359. Project 1 to N.R.M.). Topic Categories Hematopoiesis and Immune System Development (HEM)