Leptin deficiency impairs maturation of dendritic cells and enhances induction of regulatory T and Th17 cells

Authors

  • Pedro M.M. Moraes-Vieira,

    Corresponding author
    1. Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
    2. Department of Medicine, Harvard Medical School, Beth Israel Medical Deaconess Center, Transplant Institute, Boston, MA, USA
    Current affiliation:
    1. Division of Endocrinology, Diabetes and Metabolism, Beth Israel Medical Deaconess Center, Harvard Medical School, Boston, MA, USA
    • Full correspondence: Dr. Pedro M. M. Moraes Vieira, Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deacconess Medical Center, Harvard Medical School, 3 BlackFan Circle, Center of Life Science, Room 724, Boston 02115, MA, USA

      e-mail: pvieira@bidmc.harvard.edu

      Additional correspondence: Dr. Niels O. S. Camara, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil

      e-mail: niels@icb.usp.br

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  • Rafael A. Larocca,

    1. Department of Medicine, Harvard Medical School, Beth Israel Medical Deaconess Center, Transplant Institute, Boston, MA, USA
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    • These authors contributed equally to this work.

  • Enio J. Bassi,

    1. Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
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    • These authors contributed equally to this work.

  • Jean Pierre S. Peron,

    1. Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
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  • Vinícius Andrade-Oliveira,

    1. Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
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  • Frederick Wasinski,

    1. Department of Biophysics, Federal University of São Paulo, São Paulo, Brazil
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  • Ronaldo Araujo,

    1. Department of Biophysics, Federal University of São Paulo, São Paulo, Brazil
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  • Thomas Thornley,

    1. Department of Medicine, Harvard Medical School, Beth Israel Medical Deaconess Center, Transplant Institute, Boston, MA, USA
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  • Francisco J. Quintana,

    1. Harvard Medical School, Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA, USA
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  • Alexandre S. Basso,

    1. Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo, São Paulo, Brazil
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  • Terry B. Strom,

    1. Department of Medicine, Harvard Medical School, Beth Israel Medical Deaconess Center, Transplant Institute, Boston, MA, USA
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  • Niels O.S. Câmara

    Corresponding author
    1. Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
    2. Division of Nephrology, Federal University of São Paulo, São Paulo, Brazil
    • Full correspondence: Dr. Pedro M. M. Moraes Vieira, Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deacconess Medical Center, Harvard Medical School, 3 BlackFan Circle, Center of Life Science, Room 724, Boston 02115, MA, USA

      e-mail: pvieira@bidmc.harvard.edu

      Additional correspondence: Dr. Niels O. S. Camara, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil

      e-mail: niels@icb.usp.br

    Search for more papers by this author

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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