title: Leptin signaling protects NK cells from apoptosis during development in mouse bone marrow.
abstract: 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.
authors.affiliation: Departments of Pathology and Microbiology, Center of Infection and Immunology, The University of Hong Kong, Hong Kong, China.
authors.forename: Cherry Kam Chun
authors.initials: CK
authors.lastname: Lo
authors.forename: Queenie Lai Kwan
authors.initials: QL
authors.lastname: Lam
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.forename: King-Hung
authors.initials: KH
authors.lastname: Ko
authors.forename: Lingyun
authors.initials: L
authors.lastname: Sun
authors.forename: Rui
authors.initials: R
authors.lastname: Ma
authors.forename: Shengjun
authors.initials: S
authors.lastname: Wang
authors.forename: Huaxi
authors.initials: H
authors.lastname: Xu
authors.forename: Sidney
authors.initials: S
authors.lastname: Tam
authors.forename: Chang-You
authors.initials: CY
authors.lastname: Wu
authors.forename: Bo-Jiang
authors.initials: BJ
authors.lastname: Zheng
authors.forename: Liwei
authors.initials: L
authors.lastname: Lu
mesh_terms: 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
chemical_list: D020738:Leptin; D054411:Receptors, Leptin; D011994:Recombinant Proteins; C515447:leptin receptor, mouse; D016753:Interleukin-10