Total glucosides of paeony induces regulatory CD4+CD25+ T cells by increasing Foxp3 demethylation in lupus CD4+ T cells

Total glucosides of paeony (TGP), an active compound extracted from Paeony root, has been used in therapy for autoimmune diseases. However the molecular mechanism of TGP in the prevention of autoimmune response remains unclear. In this study, we found that TGP treatment significantly increased the percentage and number of Treg cells in lupus CD4+ T cells. Further investigation revealed that treatment with TGP increased the expression of Foxp3 in lupus CD4+ T cells by down-regulating Foxp3 promoter methylation levels. However, we couldn't observe similar results in healthy control CD4+ T cells treated by TGP. Moreover, our results also showed that IFN-γ and IL-2 expression was enhanced in TGP-treated lupus CD4+ T cells. These findings indicate that TGP inhibits autoimmunity in SLE patients possibly by inducing Treg cell differentiation, which may in turn be due to its ability to regulate the methylation status of the Foxp3 promoter and activate IFN-γ and IL-2 signaling.

► Treg cells in SLE patients can be induced by total glucoside of paeony (TGP). ► Foxp3, IFN-γ and IL-2 expression in lupus CD4+T cells was increased by TGP. ► TGP causes DNA demethylation of Foxp3 promoter in lupus CD4+T cells. ► We point out a novel mechanism of TGP in treatment of SLE.