Leptin deficiency impairs maturation of dendritic cells and enhances induction of regulatory T and Th17 cells |
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| Authors: | Pedro MM Moraes‐Vieira Rafael A Larocca Enio J Bassi Jean Pierre S Peron Vinícius Andrade‐Oliveira Frederick Wasinski Ronaldo Araujo Thomas Thornley Francisco J Quintana Alexandre S Basso Terry B Strom Niels OS Câmara |
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| Institution: | 1. Department of Immunology, Institute of Biomedical Sciences, University of S?o Paulo, S?o Paulo, SP, Brazil;2. Department of Medicine, Harvard Medical School, Beth Israel Medical Deaconess Center, Transplant Institute, Boston, MA, USA;3. Department of Biophysics, Federal University of S?o Paulo, S?o Paulo, Brazil;4. Harvard Medical School, Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA, USA;5. Department of Microbiology, Immunology and Parasitology, Federal University of S?o Paulo, S?o Paulo, Brazil;6. Division of Nephrology, Federal University of S?o Paulo, S?o Paulo, Brazil |
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| Abstract: | Leptin is an adipose‐secreted hormone that plays an important role in both metabolism and immunity. Leptin has been shown to induce Th1‐cell polarization and inhibit Th2‐cell responses. Additionally, leptin induces Th17‐cell responses, inhibits regulatory T (Treg) cells and modulates autoimmune diseases. Here, we investigated whether leptin mediates its activity on T cells by influencing dendritic cells (DCs) to promote Th17 and Treg‐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 DCs to induce syngeneic CD4+ T‐cell proliferation. As a consequence of this unique phenotype, DCs generated under leptin‐free conditions induced Treg or TH17 cells more efficiently than DCs 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 DCs. |
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| Keywords: | Dendritic cell (DC) Leptin Regulatory T (Treg) cells Th1 Th2 Th17 |
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