title: Leptin deficiency impairs maturation of dendritic cells and enhances induction of regulatory T and Th17 cells.
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 TH 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.
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil; Department of Medicine, Harvard Medical School, Beth Israel Medical Deaconess Center, Transplant Institute, Boston, MA, USA.
authors.forename: Pedro M M
authors.initials: PM
authors.lastname: Moraes-Vieira
authors.forename: Rafael A
authors.initials: RA
authors.lastname: Larocca
authors.forename: Enio J
authors.initials: EJ
authors.lastname: Bassi
authors.forename: Jean Pierre S
authors.initials: JP
authors.lastname: Peron
authors.forename: Vinícius
authors.initials: V
authors.lastname: Andrade-Oliveira
authors.forename: Frederick
authors.initials: F
authors.lastname: Wasinski
authors.forename: Ronaldo
authors.initials: R
authors.lastname: Araujo
authors.forename: Thomas
authors.initials: T
authors.lastname: Thornley
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Quintana
authors.forename: Alexandre S
authors.initials: AS
authors.lastname: Basso
authors.forename: Terry B
authors.initials: TB
authors.lastname: Strom
authors.forename: Niels O S
authors.initials: NO
authors.lastname: Câmara
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D016130:Immunophenotyping; D020738:Leptin / Q000172:deficiency* / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
chemical_list: D020738:Leptin
keywords: Dendritic cell (DC); Leptin; Regulatory T (Treg) cells; Th1; Th17; Th2