Involvement of leptin signaling in the survival and maturation of bone marrow-derived dendritic cells.
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.
Lam
Queenie Lai Kwan
QL
Department of Pathology and Center of Infection and Immunology, The University of Hong Kong, Hong Kong, China.
Liu
Shuxun
S
Cao
Xuetao
X
Lu
Liwei
L
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*
D020738:Leptin