Leptin Signaling Protects NK Cells from Apoptosis During Development in Mouse Bone Marrow

• DOI: 10.1038/cmi.2009.46
• Publication Date: 2010-01-07T13:08:47Z
• Authors: Cherry Kam Chun Lo; Queenie Lai Kwan Lam; Min Yang; King-Hung Ko; Lingyun Sun; Rui Ma; Shengjun Wang; Huaxi Xu; Sidney Tam; Chang-You Wu; Bo-Jiang Zheng; Liwei Lu
• Keywords: Leptin; Male; 0301 basic medicine; Cell Cycle; Apoptosis; Cell Differentiation; Mice, Mutant Strains; Recombinant Proteins; Interleukin-10; Killer Cells, Natural; Mice; 03 medical and health sciences; Lymphocyte development; Bone Marrow; Animals; Receptors, Leptin; Bone marrow; NK cell; Cell Proliferation; Signal Transduction

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.