Artesunate Attenuate Chronic Graft-Versus-Host Disease By Regulating Th17/Treg Balance

To investigate the effects of Artesunate treatment on chronic graft-versus-host disease (cGVHD). Recipient BALB/cJ mice received 8 × 10⁶ bone marrow cells with 8 × 10⁶ spleen cells from B10.D2 mice. Artesunate solubilized in acetone was injected intraperitoneally every day at the dose of 1 mg/kg at Day 28 after transplatation. The clinical scores, survival times and histopathological damage were analyzed. The frequency of Th17 and Tregs in PB and spleens from the mice was evaluated by flow cytometry. In addition, we cultured the CD4+ T cells from the spleens of mice in vitro, and stimulated these cells with artesunate, the frequency of Th17 and Tregs in these splenocytes was evaluated by flow cytometry. Artesunate administration diminishes clinical and histopathological damage and improved the survival of cGVHD mice. Artesunate contributed to Tregs development (4.45±0.04 vs 8.40±0.23; 6.62±0.24 vs 10.48±0.48; p<0.05) while decreased Th17 cells (4.45±0.04 vs 8.40±0.23; 6.62±0.24 vs 10.48±0.48; p<0.05)expressions both in PB and spleens, and decreased the Th17/Treg ratio (0.34±0.05 vs 0.09±0.03; 0.19±0.03 vs 0.06+0.02; P<0.01. Moreover, artesunate suppressed the Th17 cells expressions (0.82±0.37% vs 3.39±1.22% p<0.01) and contributed to Tregs development (34.63±1.29% vs 14.28±1.69% p<0.001), and also decreased the Th17/Treg ratio 0.24±0.09vs 0.02±0.01; p<0.05) in vitro. Artesunate suppressed the Th17 cells expressions and contributed to Tregs development. These studies provide nowsights into the artemisinin and identify artesunate as a novel drug for cGVHD.