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华支睾吸虫感染小鼠中调节性T细胞/辅助性T细胞17的动态变化及调节性T细胞/辅助性T细胞17失衡

The Dynamics of Treg/Th17 and the Imbalance of Treg/Th17 in Clonorchis sinensis-Infected Mice.

作者信息

Yan Chao, Zhang Bei-Bei, Hua Hui, Li Bo, Zhang Bo, Yu Qian, Li Xiang-Yang, Liu Ying, Pan Wei, Liu Xiang-Ye, Tang Ren-Xian, Zheng Kui-Yang

机构信息

Department of Pathogenic Biology and Immunology, Laboratory of Infection and Immunity, Xuzhou Medical College, Xuzhou 221004, Jiangsu Province, China.

出版信息

PLoS One. 2015 Nov 23;10(11):e0143217. doi: 10.1371/journal.pone.0143217. eCollection 2015.

Abstract

Clonorchiasis, caused by the liver fluke Clonorchis sinensis, is a chronic parasitic infection regulated by T cell subsets. An imbalance of CD4+CD25+ Foxp3+regulatory T (Treg) and interleukin (IL)-17-secreting T cells (Th17) may control inflammation and play an important role in the pathogenesis of immune evasion. In the present study, we assessed the dynamics of Treg/Th17 and determined whether the Treg/Th17 ratio is altered in C. sinensis-infected mice. The results showed that the percentages of splenic Treg cells in CD4+ T cells were suppressed on day 14 post-infection (PI) but increased on day 56 PI, while Th17 cells were increased on day 56 PI compared with normal control (NC) mice. The Treg/Th17 ratio steadily increased from day 28 to day 56 PI. The hepatic levels of their specific transcription factors (Foxp3 for Treg and RORγt for Th17) were increased in C. sinensis-infected mice from day 14 to 56 PI, and significantly higher than those in NC mice. Meanwhile, serum levels of IL-2 and IL-17 were profoundly increased in C. sinensis-infected mice throughout the experiment; while the concentrations of IL-6 and transforming growth factor β1 (TGF-β1) peaked on day 14 PI, but then decreased on day 28 and 56 PI. Our results provide the first evidence of an increased Treg/Th17 ratio in C. sinensis-infected mice, suggesting that a Treg/Th17 imbalance may play a role in disease outcomes of clonorchiasis.

摘要

华支睾吸虫病由肝吸虫中华支睾吸虫引起,是一种由T细胞亚群调节的慢性寄生虫感染。CD4 + CD25 + Foxp3 +调节性T(Treg)细胞和分泌白细胞介素(IL)-17的T细胞(Th17)失衡可能控制炎症,并在免疫逃避的发病机制中起重要作用。在本研究中,我们评估了Treg / Th17的动态变化,并确定了在中华支睾吸虫感染的小鼠中Treg / Th17比率是否发生改变。结果显示,感染后第14天(PI),CD4 + T细胞中脾脏Treg细胞的百分比受到抑制,但在感染后第56天增加,而与正常对照(NC)小鼠相比,Th17细胞在感染后第56天增加。从感染后第28天到第56天,Treg / Th17比率稳步上升。在中华支睾吸虫感染的小鼠中,从感染后第14天到56天,其特异性转录因子(Treg的Foxp3和Th17的RORγt)的肝脏水平升高,并且显著高于NC小鼠。同时,在整个实验过程中,中华支睾吸虫感染小鼠的血清IL-2和IL-17水平显著升高;而IL-6和转化生长因子β1(TGF-β1)的浓度在感染后第14天达到峰值,但在感染后第28天和56天下降。我们的结果首次证明了中华支睾吸虫感染小鼠中Treg / Th17比率增加,表明Treg / Th17失衡可能在华支睾吸虫病的疾病结局中起作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32c2/4658164/547872a43ea0/pone.0143217.g001.jpg

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