Chuangye Ni1, Xiaojie Gan1, Xu Li1, Han Sun2, Zhen Chen2, Hao Lu1. 1. Hepatobiliary Center, The First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China. 2. Department of Articular Orthopaedics, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China.
Abstract
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 (1α,25(OH)2D3) in the treatment of aGVHD. METHOD: An aGVHD model was built by transferring splenocytes of B6 mice into B6D2F1 mice. 1α,25(OH)2D3 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 1α,25(OH)2D3 significantly slowed aGVHD progression and improved survival of B6D2F1 recipients of grafted B6 splenocytes. 1α,25(OH)2D3 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 1α,25(OH)2D3 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 1α,25(OH)2D3 is mediated in part by improving the number of Tregs. 1α,25(OH)2D3 administration thus represents a viable approach for treating aGVHD. 2019 Annals of Translational Medicine. All rights reserved.
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 (1α,25(OH)2D3) in the treatment of aGVHD. METHOD: An aGVHD model was built by transferring splenocytes of B6 mice into B6D2F1 mice. 1α,25(OH)2D3 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 1α,25(OH)2D3 significantly slowed aGVHD progression and improved survival of B6D2F1 recipients of grafted B6 splenocytes. 1α,25(OH)2D3 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 1α,25(OH)2D3 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 1α,25(OH)2D3 is mediated in part by improving the number of Tregs. 1α,25(OH)2D3 administration thus represents a viable approach for treating aGVHD. 2019 Annals of Translational Medicine. All rights reserved.
Entities:
Keywords:
Vitamin D (VD); acute graft-versus-host disease (aGVHD); forkhead box P3 (Foxp3); regulatory T cell (Treg)