Vitamin D has immunoregulatory effects on both innate and adaptive immunity. Vitamin D has been reported to induce differentiation of monocytes into macrophages, inhibit maturation and differentiation of dendritic cells, and suppress adaptive immunity. There have been in vitro studies showing contradictory results regarding the role of vitamin D on NK cell functions, but little is known about this in vivo. The present study investigated whether vitamin D supplementation (50, 1000, or 10000 IU/kg of diet: DD, DC, or DS) affects NK cell functions in mice fed a control or high fat diet (10% or 45% kcal fat: CD or HFD) for 12 weeks. NK cell activity was assessed using radioisotope 51Cr release assay against YAC-1 target cells and splenocyte subpopulation was measured by FACS analysis. Intracellular expression of IFN-γ by NK cells, CD4+ T cells, and CD8+ T cells, and surface expression of NKG2D and CD107a were determined by FACS analysis upon stimulation of splenocytes with PMA (50 ng/mL)/ionomycin (0.5 μM) for 4 hours. The splenic NK cell activity was significantly higher in the CD-DS group than the HFD-DS group, and the CD-DS group showed significantly higher NK cell activity compared with the CD-DD and CD-DC groups, but no difference in NK cell activity was observed among the HFD groups fed different vitamin D levels. Of note, the splenic population of NK cells was significantly higher in the CD-DS group than the HFD-DS group. However, no significant differences were observed in the intracellular expression of IFN-γ and the surface expression of NKG2D and CD107a in NK cells by both dietary fat and vitamin D content. The splenic mRNA expression of Ifng and Ccl5 were significantly lower in the HFD groups compared with the CD groups, but there was no difference in the mRNA levels of Vdup1 and Vdr among the groups. Taken together, these results suggest that dietary vitamin D supplementation can modulate innate immunity by increasing NK cell activity in control mice but not in obese mice, which is presumably mediated through alternation of the splenic NK cell population.
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Differential Effects of Vitamin D Supplementation on Natural Killer Cell Activity in Normal and Obese Mice