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

Author(s):Show less -

Moraes-Vieira, Pedro M. M. ^{[1, 2]} ; Larocca, Rafael A. ^[2] ; Bassi, Enio J. ^[1] ; Peron, Jean Pierre S. ^[1] ; Andrade-Oliveira, Vinicius ^[1] ; Wasinski, Frederick ^[3] ; Araujo, Ronaldo ^[3] ; Thornley, Thomas ^[2] ; Quintana, Francisco J. ^[4] ; Basso, Alexandre S. ^[5] ; Strom, Terry B. ^[2] ; Camara, Niels O. S. ^{[6, 1]}

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo - Brazil

^[2] Harvard Univ, Sch Med, Beth Israel Med Deaconess Ctr, Dept Med, Transplant Inst, Boston, MA 02115 - USA

^[3] Univ Fed Sao Paulo, Dept Biophys, Sao Paulo - Brazil

^[4] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 - USA

^[5] Univ Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, Sao Paulo - Brazil

^[6] Univ Fed Sao Paulo, Div Nephrol, Sao Paulo - Brazil

• Document type: Journal article
• Source: European Journal of Immunology; v. 44, n. 3, p. 794-806, MAR 2014.
• Web of Science Citations: 35

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-, and IL-6, (iii) increased DC production of TGF-, 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 T(H)17 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. (AU)

• FAPESP's process: 09/50450-7 - Adipokines in experimental transplantation: interaction between leptin and the development of immunological tolerance
• Grantee: Pedro Manoel Mendes de Moraes Vieira
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 08/58564-9 - Study of adaptive immune response modulation by the sympathetic nervous system: emphasis on autoimmunity, Th17 cells and Foxp3 + regulatory T cells
• Grantee: Alexandre Salgado Basso
• Support Opportunities: Research Grants - Young Investigators Grants