Leptin protects against endotoxin-induced thymic remodeling (86.9)

Abstract

Abstract Thymic atrophy is highly inducible by stress. While prolonged thymus atrophy can contribute to T cell deficiency, no treatment is available to enhance thymopoiesis during stress events. Leptin deficiency in mice results in chronic thymic atrophy and suppressed immunity, suggesting a role for leptin in regulating immune homeostasis. Specific roles however for intrathymic leptin signaling are currently undefined. We report here the novel finding that leptin receptor expression in the thymus is not present on developing thymocytes, but restricted to medullary thymic epithelial cells. We found leptin protected against endotoxin-induced acute thymic atrophy by preventing the loss of medullary thymic epithelial cells, protecting DP thymocytes from endotoxin-induced apoptosis, and increasing proliferation in DN thymocytes. We demonstrated that these thymoprotective effects are mediated through a leptin receptor isoform b-specific mechanism, and that leptin treatment increased thymic steady-state mRNA levels for IL-7. Taken together, our data suggested a novel intrathymic role for leptin in indirectly modulating thymocytes during thymic injury via a direct effect on medullary thymic epithelial cells. Overall, these findings support the use of leptin as a potential therapeutic to enhance T cell reconstitution in settings of stress-induced thymic atrophy. Supported by AG025150.