Vitamin D alleviates acute graft-versus-host disease through promoting the generation of Foxp3+ T cells

Background: Acute graft-versus-host disease (aGVHD) is a medical complication which may result in significant morbidity and mortality after transplantation. The aim of this study investigated the therapeutic effect and underlying mechanism of 1,25-dihydroxyvitamin D3 (1 alpha,25(OH)(2)D-3) in the treatment of aGVHD. Method: An aGVHD model was built by transferring splenocytes of B6 mice into B6D2F1 mice. 1 alpha,25(OH)(2)D-3 was added to evaluate the protective function to aGVHD; the phenotype and cytokine expression profile of spleen cells from the aGVHD model were determined using flow cytometry 2 weeks after the model is established. Result: Administration of 1 alpha,25(OH)(2)D-3 significantly slowed aGVHD progression and improved survival of B6D2F1 recipients of grafted B6 splenocytes. 1 alpha, 25(OH)(2)D-3 treatment also resulted in an increased number of CD4(+)Foxp3(+) regulatory T cells (Tregs) but decreased the number of CD4(+)IL-4(+) cells. In vitro analysis demonstrated that 1 alpha,25(OH)(2)D-3 directly increased forkhead box P3 (Foxp3) and IL-10 expression and enhanced the function of induced Tregs (iTregs). Conclusions: This analysis indicated that the effect of 1 alpha,25(OH)(2)D-3 is mediated in part by improving the number of Tregs. 1 alpha,25(OH)(2)D-3 administration thus represents a viable approach for treating aGVHD.