Involvement of leptin signaling in the survival and maturation of bone marrow-derived dendritic cells

Eur J Immunol. 2006 Dec;36(12):3118-30. doi: 10.1002/eji.200636602.

Abstract

Previous studies demonstrated that lymphocyte development is impaired in leptin receptor (Ob-R)-deficient db/db mice. However, it remains unclear whether or not leptin signaling plays a physiological role in dendritic cell (DC) development and function. In this study, we first detected Ob-R expression in murine DC. Using db/db mice at a pre-diabetic stage, we demonstrate that the total number of DC generated from bone marrow (BM) cultures is significantly lower than in WT controls. Similarly, selective blockade of leptin with a soluble mouse Ob-R chimera (Ob-R:Fc) inhibited DC generation in wild-type BM cultures. The reduced DC yield in db/db BM culture was attributed to significantly increased apoptosis, which was associated with dysregulated expression of Bcl-2 family genes. Moreover, db/db DC displayed markedly reduced expression of co-stimulatory molecules and a Th2-type cytokine profile, with a poor capacity to stimulate allogeneic T cell proliferation. Consistent with their impaired DC phenotype and function, db/db DC showed significantly down-regulated activities of the PI3K/Akt pathway as well as STAT-3 and IkappaB-alpha. In conclusion, our findings demonstrate the involvement of leptin signaling in DC survival and maturation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology*
  • Bone Marrow Cells / metabolism
  • Cell Differentiation / immunology*
  • Cell Survival / immunology
  • Dendritic Cells / cytology*
  • Dendritic Cells / metabolism
  • Leptin / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Signal Transduction / immunology*

Substances

  • Leptin