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Leptin deficiency impairs maturation of dendritic cells and enhances induction of regulatory T and T h17 cells

2013; Wiley; Volume: 44; Issue: 3 Linguagem: Inglês

10.1002/eji.201343592

1521-4141

Pedro M. Moraes‐Vieira, Rafael A. Larocca, Ênio José Bassi, Jean Pierre Schatzmann Peron, Vinícius Andrade‐Oliveira, Frederick Wasinski, Ronaldo C. Araújo, Thomas B. Thornley, Francisco J. Quintana, Alexandre S. Basso, Terry B. Strom, Niels Olsen Saraiva Câmara,

Biochemical Analysis and Sensing Techniques

Leptin is an adipose‐secreted hormone that plays an important role in both metabolism and immunity. Leptin has been shown to induce T h1‐cell polarization and inhibit T h2‐cell responses. Additionally, leptin induces T h17‐cell responses, inhibits regulatory T ( T reg) cells and modulates autoimmune diseases. Here, we investigated whether leptin mediates its activity on T cells by influencing dendritic cells ( DC s) to promote T h17 and T reg‐cell immune responses in mice. We observed that leptin deficiency (i) reduced the expression of DC maturation markers, (ii) decreased DC production of IL ‐12, TNF ‐α, and IL ‐6, (iii) increased DC production of TGF ‐β, and (iv) limited the capacity of DC s to induce syngeneic CD 4 + T ‐cell proliferation. As a consequence of this unique phenotype, DC s generated under leptin‐free conditions induced T reg or T H 17 cells more efficiently than DC s generated in the presence of leptin. These data indicate important roles for leptin in DC homeostasis and the initiation and maintenance of inflammatory and regulatory immune responses by DC s.