Abstract 757: Defective Leptin Signaling Improves Regulatory T Cell Immune Response And Protects Mice From Atherosclerosis
Obesity is a major risk factor for atherosclerosis and is associated with increased cardiovascular morbidity and mortality but the precise molecular pathways responsible for this close association remain poorly understood. Leptin, a hormone that increases with obesity was suggested to play direct roles in the modulation of the immune response that may participate to development of cardiovascular diseases. In this study, we report that leptin deficient atherosclerotic-prone mice (ldlr−/ − ob/ob) induces 6-fold reduction of atherosclerotic lesions than (ldlr−/ −) mice with similar cholesterol levels. Besides, ldlr−/ − ob/ob mice show enhanced expression of Foxp3, the specification transcription factor of regulatory T (Treg) cells, and improved Treg cell function. Leptin receptor-deficient (db/db) mice display marked increase in both the number and the suppressive function of Treg cells. Supplementation of Treg-deficient lymphocytes with Treg cells from db/db mice in an experimental model of atherosclerosis induces a significant reduction of lesion size and inhibits interferon-γ expression, compared with supplementation by Treg cells from wild type mice. These results identify a critical role for leptin/leptin receptor pathway in the modulation of the regulatory immune response in atherosclerosis, and suggest that alteration in regulatory immunity may predispose obese individuals to atherosclerosis.