Artesunate attenuate chronic graft-versus-host disease by regulating Th17/Treg balance.
10.3760/cma.j.issn.0253-2727.2019.01.012
- Author:
Xiao Mei CHEN
1
;
Jian Yu WENG
;
Pei Long LAI
;
Yu Lian WANG
;
Xin HUANG
;
Su Xia GENG
;
Li Yan GUO
;
Tian HUANG
;
Ling Ji ZENG
;
Xin DU
Author Information
1. Department of Hematology, Guangdong General Hospital/Guangdong Academy of Medical Sciences, Guangdong Geriatrics Institute, Guangzhou 510080, China.
- Publication Type:Journal Article
- Keywords:
Artesunate;
Chronic graft-versus-host disease;
Regulatory T cells;
Th17 cells;
Th17/Treg balance
- MeSH:
Animals;
Artesunate;
Graft vs Host Disease;
Mice;
Mice, Inbred BALB C;
T-Lymphocytes, Regulatory;
Th17 Cells
- From:
Chinese Journal of Hematology
2019;40(1):63-68
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the effects of artesunate treatment on chronic graft-versus-host disease (cGVHD). Methods: Recipient BALB/c mice received 8 × 10(6) bone marrow cells with 8×10(6) spleen cells from B10D2 mice. Artesunate solubilized in acetone was injected intraperitoneally every day at the dose of 1 mg/kg at Day 28 after BMT. The clinical scores, survival and histopathological damage were analyzed. The frequency of Th17 and Tregs in PB and spleens from the mice were evaluated by flow cytometry. In addition, CD4(+) T cells from the spleens of mice were cultured in vitro, then stimulated with artesunate, the frequency of Th17 and Tregs in these splenocytes were evaluated by flow cytometry. Results: Artesunate administration diminished clinical and histopathological damage, and improved the survival of cGVHD mice[(46.57±7.83)% vs (55.71±6.99)%, χ(2)=5.457, P=0.020]; Artesunate contributed to Tregs development [(4.45±0.04)% vs (8.40±0.23)%, t=15.679, P<0.001; (6.62±0.24)% vs (10.48±0.48)%, t=6.587, P=0.003] while decreased Th17 cells [(1.51±0.18)% vs (0.58±0.19)%, t=7.233, P<0.001; (1.48±0.38)% vs (0.71±0.18)%, t=3.653, P=0.011] expressions in both PB and spleens, and decreased the Th17/Treg ratio (0.34±0.05 vs 0.09±0.03, t=7.621, P=0.002; 0.19±0.03 vs 0.06±0.02, t=6.993, P=0.002). Moreover, artesunate suppressed the Th17 cells expressions [(0.82±0.37) % vs (3.39±1.22) %, t=4.044, P=0.007] and contributed to Tregs development [(34.63±1.29) % vs (14.28±1.69) %, t=19.119, P<0.001], and also decreased the Th17/Treg ratio (0.24±0.09 vs 0.02±0.01, t=4.780, P=0.003) in vitro. Conclusions: Artesunate suppressed the Th17 cells expressions and contributed to Tregs development, which provided new sights into the development of a novel drug for cGVHD, e.g., artemisinin.
