Leptin deficiency in vivo enhances the ability of splenic dendritic cells to activate T cells

摘要

Leptin is a pleiotropic adipokine that is critical for regulating food intake and energy expenditure and also participates in functions of the immune system, including those of antigen-presenting cells. Here, we assess the effect of leptin deficiency on the function splenic dendritic cells (sDC). sDC from leptin-deficient mice (Lep^ob) were evaluated ex vivo for phenotype, ability to respond to inflammatory stimuli, to acquire and process antigens and to activate T cells. The data show that Lep^ob sDC express activation markers similar to controls and respond similarly to LPS activation or anti-CD40 cross-linking. In addition, antigen acquisition and processing by Lep^ob sDC was similar to controls. However, Lep^ob sDC elicited higher production of IFN-γ in mixed lymphocyte reactions and increased production of IL-2 by antigen-specific T-cell hybridoma relative to controls. To assess Lep^ob sDC activation of T cells in vivo, Lep^ob and control mice were infected systemically with Mycobacterium avium. Lep^ob mice were significantly better at neutralizing the infection as measured by splenic bacterial load over time. This was mirrored with an increased percentage of activated T cells in M. avium-infected Lep^ob mice. Thus, although no changes were detected in sDC phenotype, activation, antigen processing or presentation, these DC surprisingly presented an enhanced ability to activate T cells ex vivo and in vivo. These data demonstrate that leptin can modulate DC function and suggest that leptin may dampen T-cell responsiveness in the physiological setting.