Leptin signaling protects NK cells from apoptosis during development in mouse bone marrow.
Increasing evidence indicates a role of leptin in immune response, but it remains largely unclear whether leptin signaling is involved in regulating NK cell development in the bone marrow (BM). In this study, we have characterized NK cell differentiation and maturation in the BM of leptin-receptor deficient db/db mice at a prediabetic stage. Although the BM cellularity was similar to the control value, the total number of NK cells was severely reduced in mutant mice. Flow cytometric analysis of db/db BM cells revealed significantly decreased frequencies of developing NK cells at various stages of differentiation. BM db/db NK cells displayed markedly increased apoptosis but maintained normal cell cycling status and proliferative capacity. Moreover, recombinant leptin could significantly enhance the survival of NK cells from wild-type mice in cultures. Further examination on NK cell functional activity showed that db/db NK cells exhibited normal intrinsic cytotoxicity with significantly increased IL-10 production. Taken together, our findings suggest that leptin signaling regulates NK cell development via enhancing the survival of immature NK cells in mouse BM.
Lo
Cherry Kam Chun
CK
Departments of Pathology and Microbiology, Center of Infection and Immunology, The University of Hong Kong, Hong Kong, China.
Lam
Queenie Lai Kwan
QL
Yang
Min
M
Ko
King-Hung
KH
Sun
Lingyun
L
Ma
Rui
R
Wang
Shengjun
S
Xu
Huaxi
H
Tam
Sidney
S
Wu
Chang-You
CY
Zheng
Bo-Jiang
BJ
Lu
Liwei
L
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001853:Bone Marrow / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D016753:Interleukin-10 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000473:pathology / Q000502:physiology*; D020738:Leptin / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D054411:Receptors, Leptin / Q000037:antagonists & inhibitors / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction
D020738:Leptin; D054411:Receptors, Leptin; D011994:Recombinant Proteins; C515447:leptin receptor, mouse; D016753:Interleukin-10