Deviated balance between Th1 and Th17 cells exacerbates acute graft-versus-host disease in mice
Deviated balance between Th1 and Th17 cells exacerbates acute graft-versus-host disease in mice
复制标题
Th1 和 Th17 细胞之间的平衡失调会加剧小鼠的急性移植物抗宿主病
DOI：
10.1016/j.cyto.2014.04.002
复制
发表时间：
2014-08-01
期刊：
影响因子：
3.8
通讯作者：
Xu, Kailin
中科院分区：
文献类型：
--
作者：
Pan, Bin;Zhang, Ying;Xu, Kailin
背景：Th1/Th17 失衡已被证明可介导多种炎症性疾病。我们推断 Th1/Th17 失衡也可能导致急性移植物抗宿主病 (GVHD) 的发病机制。本研究旨在探讨Th1/Th17失衡与急性GVHD之间的关系。方法：我们将C57BL/6（H-2（b））供体的小鼠GVHD模型应用于BALB/c（H-2（d））受体，通过用低剂量的卤常酮（HF）治疗受体，HF能够选择性地抑制Th17分化并促进Th1分化。监测受体小鼠的存活率、体重变化、临床症状和急性GVHD的病理证据。我们还测量了循环中Th1和Th17细胞的比例以及GVHD相关组织中IFN-γ和IL-17A的表达水平。结果：首先，我们证实急性GVHD中存在Th1/Th17失衡，并且Th1/Th17失衡与急性GVHD的严重程度呈正相关。其次，低剂量的 HF 通过将 Th1/Th17 平衡驱动至 Th1 主导反应，从而加剧 Th1/Th17 失衡。最后，Th1/Th17 失衡加剧导致全身 GVHD 加重。 Th1型反应增加导致肝脏和肠道GVHD加重，抑制Th17分化足以减轻肺损伤。结论：我们的研究表明Th1/Th17失衡在小鼠GVHD发病机制中发挥着关键作用。 (C) 2014 Elsevier Ltd. 保留所有权利。
Background: Th1/Th17 imbalance had been indicated to mediate several kinds of inflammatory diseases. We deduce that Th1/Th17 imbalance might also contribute to the pathogenesis of acute graft-versus-host disease (GVHD). This study is to investigate the relation between Th1/Th17 imbalance and acute GVHD.Methods: We applied a murine GVHD model of C57BL/6 (H-2(b)) donor to BALB/c (H-2(d)) recipient by treating the recipients with low dose of halofuginone (HF), which is competent in selectively inhibiting Th17 differentiation and facilitating Th1 differentiation. Recipient mice were monitored for survival rate, body weight change, clinical symptoms and pathological evidence of acute GVHD. We also measured the proportions of Th1 and Th17 cells in circulation and expression levels of IFN-gamma, and IL-17A in tissues involved in GVHD.Results: Firstly, we confirm the existence of Th1/Th17 imbalance in acute GVHD and Th1/Th17 imbalance positively correlates with severity of acute GVHD. Secondly, low dose of HF augments Th1/Th17 imbalance by driving the Th1/Th17 balance to a Th1-dominant reaction. Finally, augmented Th1/Th17 imbalance leads to aggravated systemic GVHD. An increased Th1-type reaction results in aggravated hepatic and intestinal GVHD, and inhibiting Th17 differentiation is sufficient to alleviate pulmonic impairment.Conclusion: Our study is indicative for a critical role of Th1/Th17 imbalance in the pathogenesis of murine GVHD. (C) 2014 Elsevier Ltd. All rights reserved.