Thymic Epithelial Cell Support of Thymopoiesis Does Not Require .

Age-related thymic involution is characterized by a decrease in thymic epithelial cell (TEC) number and function parallel to a disruption in their spatial organization, resulting in defective thymocyte development and proliferation as well as peripheral T cell dysfunction. Deficiency of , an antiaging gene and modifier of fibroblast growth factor signaling, causes premature aging. To investigate the role of in accelerated age-dependent thymic involution, we conducted a comprehensive analysis of thymopoiesis and peripheral T cell homeostasis using -deficient () mice. At 8 wk of age, mice displayed a severe reduction in the number of thymocytes (10-100-fold reduction), especially CD4 and CD8 double-positive cells, and a reduction of both cortical and medullary TECs. To address a cell-autonomous role for in TEC biology, we implanted neonatal thymi from -deficient and -sufficient mice into athymic hosts. thymus grafts supported thymopoiesis equivalently to -sufficient thymus transplants, indicating that is not intrinsically essential for TEC support of thymopoiesis. Moreover, lethally irradiated hosts given or wild-type bone marrow had normal thymocyte development and comparably reconstituted T cells, indicating that is not inherently essential for peripheral T cell reconstitution. Because mice have higher levels of serum phosphorus, calcium, and vitamin D, we evaluated thymus function in mice fed with a vitamin D-deprived diet. We observed that a vitamin D-deprived diet abrogated thymic involution and T cell lymphopenia in 8-wk-old mice. Taken together, our data suggest that deficiency causes thymic involution via systemic effects that include high active vitamin D levels.