Leptin Directly Protects Thymus Tissue from Endotoxin-induced Involution (85.9)

Abstract Thymus tissue produces new T cells and functions well into adulthood. Thymus tissue is highly susceptible to atrophy induced by stress, infections, and ionizing radiation. Prolonged thymus atrophy can contribute to T cell deficiency or prevent immune recovery after acute T cell depletion. No treatment however is currently available to protect against thymus involution. Leptin is a naturally occurring metabolic hormone currently used therapeutically for obesity. We have previously reported that leptin protects against bacterial endotoxin-induced thymus atrophy in a lipopolysaccharide (LPS) mouse model resulting in increased thymus weight, cellularity, and T cell receptor gene rearrangement. We now report the mechanism by which leptin protects the thymus from acute involution. Leptin directly relieves the LPS-induced block on proliferation in CD4−/CD8− thymocytes and protects against stress-induced CD4+/CD8+ thymocyte apoptosis (9% vs. 34% in control, p < 0.01) in a Bcl-2 independent manner. Taken together, these data demonstrate that leptin directly protects against thymus atrophy by promoting expansion of CD4−/CD8− thymocytes and blocking death of CD4+/CD8+ thymocytes. Together, these data support further investigation of leptin as a therapeutic for stimulating thymic function in settings of stress. Supported by the NIH PO1-HL67314, RO1-AG025150.