Yao Yao, Pan Bin, Bian Yue-Ping, Xia Dan-Dan, Cheng Hai, Song Guo-Liang, Zeng Ling-Yu, Xu Kai-Lin
Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China.
Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China. E-mail:
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2015 Oct;23(5):1488-92. doi: 10.7534/j.issn.1009-2137.2015.05.051.
To investigate the effects of Th1/Th17 cell imbalance on the pathogenesis of acute graft-versus-host disease (GVHD) in mice.
In a murine GVHD model of C57BL/6 (H-2(b)), a low dose of halofuginone (HF) was applied for treating the recipients in order to result in Th1/Th17 imbalance. Rechipient mice were divided into GVHD group (without HF intervention) and GVHD plus HF group (treated by HF). The recipients were monitored for survival rate, clinical scores of acute GVHD, contents of circulatory Th1 and Th17 cells, Th1/Th17 ratio and serum level of IFN-γ and IL-17A. Expression levels of IFN-γ and IL-17A in target organs were analyzed by using real-time PCR, and the target organs were delivered for histological examinations.
Recipients treated with HF showed that all the mortality, circulatory Th1/Th17 ratio and clinical score were higher than those in the mice without HF intervention (P < 0.05). Circulatory Th1/Th17 ratio positively correlates with clinical score (P < 0.001). HF administration reduces the expression level of intestinal IL-17A and increases intrahepatic and intestinal IFN-γ level (P < 0.05), HF treatment aggravates GVHD in liver and small intestine with augmented hepatic and intestinal inflammation.
Th1/Th17 imbalance contributes to the pathogenesis of acute GVHD.
探讨Th1/Th17细胞失衡对小鼠急性移植物抗宿主病（GVHD）发病机制的影响。
在C57BL/6（H-2(b)）小鼠GVHD模型中，给予低剂量常山酮（HF）处理受体小鼠以导致Th1/Th17失衡。将受体小鼠分为GVHD组（无HF干预）和GVHD+HF组（HF处理）。监测受体小鼠的存活率、急性GVHD临床评分、循环中Th1和Th17细胞含量、Th1/Th17比值以及血清IFN-γ和IL-17A水平。采用实时PCR分析靶器官中IFN-γ和IL-17A的表达水平，并对靶器官进行组织学检查。
接受HF处理的受体小鼠显示，所有死亡率、循环中Th1/Th17比值和临床评分均高于未接受HF干预的小鼠（P<0.05）。循环中Th1/Th17比值与临床评分呈正相关（P<0.001）。给予HF可降低肠道IL-17A表达水平，并增加肝内和肠道IFN-γ水平（P<0.05），HF处理加重肝脏和小肠的GVHD，伴有肝脏和肠道炎症加剧。
Th1/Th17失衡促成急性GVHD的发病机制。
