Artesunate influences Th17/Treg lymphocyte balance by modulating Treg apoptosis and Th17 proliferation in a murine model of rheumatoid arthritis

Abstract

CD4 ⁺ regulatory T (Treg) cells and T-helper 17 (Th17) cells have been shown to have important roles in rheumatoid arthritis (RA). In our previous study, it was demonstrated that artesunate was able to alter the Treg/Th17 ratio in patients with RA; however, the underlying mechanisms remain unclear. The present study established a male Sprague Dawley (SD) rat model of type II collagen-induced arthritis (CIA). SD rats were divided into normal control, CIA model and artesunate-treated (5, 10 or 20 mg/kg/day) groups. Treg and Th17 cells were detected in the synovium by immunohistochemical analysis of forkhead/winged helix transcription factor (Foxp3) and interleukin (IL)-17 expression. Subsequently, lymphocytes were extracted from the rat spleens, and the proportions of Treg/Th17 cells were detected by flow cytometry. The results demonstrated that the expression levels of Foxp3 were significantly decreased, and those of IL-17 were significantly increased, in the CIA model group, as compared with the normal control group. The results demonstrated that artesunate decreased the frequency of Th17 cells and increased the frequency of Treg cells in CIA rats in a dose-dependent manner. In conclusion, the present study suggested that artesunate may regulate the Th17/Treg balance by inducing Th17-mediated apoptosis. Therefore, artesunate may be considered a novel therapeutic agent for the treatment of patients with RA.