Role of leptin signaling in regulating NK cell development in mouse bone marrow (89.21)

Abstract

Abstract Increasing evidence suggests that leptin is involved in regulating immune response by acting as a growth factor on lymphocytes. Previous studies showed reduced number of NK cells in various peripheral organs of leptin-receptor-deficient db/db mice. However, it remains unknown whether leptin-receptor signaling is involved in regulating NK cell development in the bone marrow (BM). In this study, we characterized NK cell development in the BM of db/db mice at a prediabetic stage. Total number of NK cells was moderately reduced in the BM of mutant mice whereas both frequencies and total numbers of NK cell subpopulations were significantly reduced at various differentiation stages. Moreover, BM NK cells from db/db mice displayed markedly increased apoptosis but did not show any defects in cell cycling status and proliferative capacity. Consistently, recombinant leptin could significantly enhance the survival of NK cells of wild-type mice. To verify if NK cell functional activity was impaired in db/db mice, sorting-purified splenic DX5+CD3− NK cells were evaluated for their cytotoxicity and rmIL-15-induced proliferation capacity. Interestingly, db/db NK cells showed unimpaired capacities in their proliferation and cytotoxic function. In conclusion, our findings demonstrate that leptin-receptor deficiency impairs NK cell development in the db/db mouse BM via affecting NK cell survival. This work was supported by grants from the Research Grants Council of Hong Kong (HKU7423/04M).