Dietary vitamin D3 supplementation enhances splenic NK cell activity in healthy and diabetic male mice

Type 2 diabetes mellitus negatively affects the immune system, resulting in reduced natural killer (NK) cell activity. Vitamin D has been shown to regulate innate and adaptive immune cells. However, the effects of vitamin D on NK cells remain inconclusive, especially in the context of diabetes. We hypothesized that dietary vitamin D₃ supplementation can enhance NK cell activity in diabetic mice. Therefore, we investigated the effects of dietary vitamin D₃ on NK cell activity in control and diabetic mice and explored the mechanisms of NK cell activity modulation by vitamin D₃. Control (CON) and diabetic mice (db/db) were randomly divided into 2 groups, then fed either a control diet (948 IU vitamin D₃/kg diet, vDC) or a diet supplemented with vitamin D₃ (9,477 IU vitamin D₃/kg diet, vDS) for 8 weeks. Diabetic mice exhibited lower NK cell activity than control mice. The vDS group had significantly higher NK cell activity than the vDC group in both control and diabetic mice. The vDS group had a higher percentage of CD11b single-positive NK cells than the vDC group (CON-vDS 34%; db/db-vDS 30%; CON-vDC 27%; db/db-vDC 22%). The intracellular expression of splenic TGF-β was significantly higher in the db/db group than in the CON group. Overall, vDS group had higher Bcl2 and Tbx21 mRNA expressions than the vDC group. In conclusion, the present study shows that NK cell activity is impaired under diabetic conditions, possibly due to the reduced percentage of mature NK cells. Moreover, NK activity is enhanced by dietary supplementation in both control and diabetic mice that may be associated with changes in the proportion of mature NK cells.