Dioscin Restores Immunological Tolerance of CD4+CD25+ Regulatory T Cells in Aplastic Anemia Mouse Model

Abstract

Abstract Background: Aplastic anemia (AA) is an immune-mediated disease of bone marrow failure owing to activated cytotoxic T lymphocytes (CTLs). CD4+CD25+ regulatory T cells (Tregs) could negatively regulate CTLs to maintain self-tolerance and avoid excessive immune responses. This study aims to investigate the effect of Dioscin on the functions of CD4+CD25+ Tregsin the AA mouse model, which were induced by total body irradiation and allogeneic lymphocyte infusion. Methods and Results: The collected CD4+CD25+Tregs were randomly divided into 5 groups: 1) normal control group, 2) aplastic anemia model group, 3) Dioscin group, 4) Cyclosporine A group, 5) Triptolide group. Based on flow cytometry and qRT-PCR, forkhead box P3 (Foxp3), cytotoxic T lymphocyte-associated antigen 4 (CTLA4) and glucocorticoid-induced tumor necrosis factor-related protein (GITR) were quantified to evaluate the function expression of CD4+CD25+ Tregs. Conclusions: The result shows that the AA mice manifested loss of Foxp3 and CTLA4 expressions and overexpression of GITR. It also shows that compared with traditional AA medicine such as Cyclosporine A and Triptolide, Dioscin displays better efficacy in promoting Tregs differentiation by affecting CTLA4 and GITR on the surface of Tregs and restoring the expression of Foxp3.