Triptolide ameliorates lupus via the induction of miR-125a-5p mediating Treg upregulation

Triptolide is a biologically active component of the Chinese antirheumatic herbal remedy Tripterygium wilfordii Hook F, which has been shown to be effective in treating murine lupus. However, its immunological mechanisms are poorly understood. Regulatory T cells (Treg) are pivotal for maintaining peripheral self-tolerance and controlling autoimmunity. This study was undertaken to examine the therapeutic effect of triptolide in lupus mice and the related molecular mechanisms. Our results showed that triptolide treatment ameliorated serum anti-dsDNA, proteinuria and renal histopathologic assessment in MRL/lpr mice, induced the miR-125a-5p expression and enhanced the proportion of Treg in vivo. In vitro, triptolide upregulated the proportion of Treg and the miR-125a-5p expression. Down-regulation of the miR-125a-5p expression reversed the effect of triptolide on Treg. In conclusion, triptolide could induce Treg and the miR-125a-5p expression in vivo and in vitro. Inhibiting the effect of miR-125a-5p could counteract the effect of triptolide on inducing Treg. The study has strong implications for the therapeutic applications of triptolide in systemic lupus erythematosus.