title: Leptin promotes systemic lupus erythematosus by increasing autoantibody production and inhibiting immune regulation.
abstract: Leptin is an adipocytokine that plays a key role in the modulation of immune responses and the development and maintenance of inflammation. Circulating levels of leptin are elevated in systemic lupus erythematosus (SLE) patients, but it is not clear whether this association can reflect a direct influence of leptin on the propathogenic events that lead to SLE. To investigate this possibility, we compared the extent of susceptibility to SLE and lupus manifestations between leptin-deficient (ob/ob) and H2-matched leptin-sufficient (wild-type, WT) mice that had been treated with the lupus-inducing agent pristane. Leptin deficiency protected ob/ob mice from the development of autoantibodies and renal disease and increased the frequency of immunoregulatory T cells (Tregs) compared with leptin-sufficient WT mice. The role of leptin in the development of SLE was confirmed in the New Zealand Black (NZB) × New Zealand White (NZW)F1 (NZB/W) mouse model of spontaneous SLE, where elevated leptin levels correlated with disease manifestations and the administration of leptin accelerated development of autoantibodies and renal disease. Conversely, leptin antagonism delayed disease progression and increased survival of severely nephritic NZB/W mice. At the cellular level, leptin promoted effector T-cell responses and facilitated the presentation of self-antigens to T cells, whereas it inhibited the activity of regulatory CD4 T cells. The understanding of the role of leptin in modulating autoimmune responses in SLE can open possibilities of leptin-targeted therapeutic intervention in the disease.
authors: Department of Medicine, University of California, Los Angeles, CA 90095;
authors: Elaine V
authors: EV
authors: Lourenço
authors: Department of Medicine, University of California, Los Angeles, CA 90095;
authors: Aijing
authors: A
authors: Liu
authors: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, 80131 Naples, Italy; Istituto di Endocrinologia e Oncologia Sperimentale-Consiglio Nazionale delle Ricerche, 80131 Naples, Italy.
authors: Giuseppe
authors: 0000-0001-9429-0616
authors: G
authors: Matarese
authors: Department of Medicine, University of California, Los Angeles, CA 90095; ALaCava@mednet.ucla.edu.
authors: Antonio
authors: A
authors: La Cava
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000235:genetics*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D020738:Leptin / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000627:therapeutic use; D008180:Lupus Erythematosus, Systemic / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008814:Mice, Inbred NZB; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D013729:Terpenes / Q000633:toxicity
chemical_list: D001323:Autoantibodies; D020738:Leptin; D013729:Terpenes; C009042:pristane
keywords: animal models; autoimmunity; immune regulation; leptin; systemic lupus erythematosus