Leptin is a hormone primarily involved in the regulation of basal metabolism that also has an important role in immune responses. Leptin promotes inflammation and can accelerate onset and progression of several autoimmune diseases including systemic lupus erythematosus (SLE). Because of that, we will test whether leptin-based intervention may be beneficial for the course of SLE in a mouse model of SLE, the (NZB x NZW)F1 (NZB/W F1) mouse. Since we hypothesize that leptin affects the phenotype and function of some immune-cell subsets and intereferes/promotes the release of soluble mediators in order to exert its propathogenic effects in SLE, we will dissect several cellular and molecular events induced by leptin in NZB/W F1 mice. We will study the effects of leptin on autoreactive T cells and will characterize some intracellular signaling events induced by leptin. We will then test different approaches of leptin-based intervention in these mice to ultimately set the stage for translational studies to humans. By defining some crucial aspects related to the physiopathology of leptin in the development of systemic autoimmunity in NZB/W F1 mice, these studies will explore new strategies of therapeutic intervention in lupus mice for future translational research in humans aimed at improving management of this incurable disease.
| La Cava, Antonio (2009) Natural Tregs and autoimmunity. Front Biosci (Landmark Ed) 14:333-43 |
| Gianfrani, Carmen; Troncone, Riccardo; La Cava, Antonio (2008) Autoimmunity and celiac disease. Mini Rev Med Chem 8:129-34 |
| La Cava, A (2008) T-regulatory cells in systemic lupus erythematosus. Lupus 17:421-5 |
| Matarese, Giuseppe; De Rosa, Veronica; La Cava, Antonio (2008) Regulatory CD4 T cells: sensing the environment. Trends Immunol 29:12-7 |
| Matarese, Giuseppe; Mantzoros, Christos; La Cava, Antonio (2007) Leptin and adipocytokines: bridging the gap between immunity and atherosclerosis. Curr Pharm Des 13:3676-80 |
| Singh, Ram Pyare; La Cava, Antonio; Wong, Maida et al. (2007) CD8+ T cell-mediated suppression of autoimmunity in a murine lupus model of peptide-induced immune tolerance depends on Foxp3 expression. J Immunol 178:7649-57 |
| Ferrera, Francesca; Hahn, Bevra H; Rizzi, Marta et al. (2007) Protection against renal disease in (NZB x NZW)F(1) lupus-prone mice after somatic B cell gene vaccination with anti-DNA immunoglobulin consensus peptide. Arthritis Rheum 56:1945-53 |
| Matarese, G; Leiter, E H; La Cava, A (2007) Leptin in autoimmunity: many questions, some answers. Tissue Antigens 70:87-95 |
| De Rosa, Veronica; Procaccini, Claudio; Cali, Gaetano et al. (2007) A key role of leptin in the control of regulatory T cell proliferation. Immunity 26:241-55 |
| La Cava, Antonio; Shi, Fu-Dong (2006) Natural and adaptive immune cell-based therapies in autoimmunity. Curr Med Chem 13:1557-66 |
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