title: Involvement of leptin signaling in the survival and maturation of bone marrow-derived dendritic cells.
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.
authors.affiliation: Department of Pathology and Center of Infection and Immunology, The University of Hong Kong, Hong Kong, China.
authors.forename: Queenie Lai Kwan
authors.initials: QL
authors.lastname: Lam
authors.forename: Shuxun
authors.initials: S
authors.lastname: Liu
authors.forename: Xuetao
authors.initials: X
authors.lastname: Cao
authors.forename: Liwei
authors.initials: L
authors.lastname: Lu
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D002470:Cell Survival / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism; D020738:Leptin / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D020738:Leptin