The Th17/Treg functional imbalance during atherogenesis in ApoE-/- mice
The Th17/Treg functional imbalance during atherogenesis in ApoE-/- mice
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DOI：
10.1016/j.cyto.2009.09.007
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发表时间：
2010-02-01
期刊：
影响因子：
3.8
通讯作者：
Cheng, Xiang
中科院分区：
文献类型：
--
作者：
Xie, Jiang-jiao;Wang, Jun;Cheng, Xiang
目的：动脉粥样硬化是一种由T淋巴细胞亚群调控的慢性炎症性疾病。最近，CD4(+) CD25(+) Foxp3（+）调节性T （Treg）细胞和Th17细胞被描述为两个不同的亚群，在自身免疫中具有相反的作用。临床观察发现，急性冠脉综合征患者存在Th17/Treg失衡。我们研究了ApoE（-/-）小鼠动脉粥样硬化过程中是否存在Th17/Treg功能失衡。方法与结果：比较ApoE（-/-）小鼠与年龄匹配的C57BL/6J小鼠不同水平的Th17/Treg功能，包括细胞频率、相关细胞因子分泌和关键转录因子。结果表明，ApoE（-/-）小鼠与年龄匹配的C57BL/6J小鼠相比，Th17相关细胞因子（IL-17和IL-6）分泌和转录因子（ROR γ t）表达水平显著升高，Treg细胞数量、Treg相关细胞因子（tgf - β(1)）分泌和转录因子（Foxp3）表达水平明显降低。Th17相关介质在ApoE（-/-）小鼠的早期（8-16周龄）达到最大表达值，随后其表达水平持续下降。与此同时，ApoE（-/-）小鼠中Treg相关介质的表达比同龄野生型小鼠低得多。结论：ApoE（-/-）小鼠在动脉粥样硬化发生过程中存在Th17/Treg功能失衡，提示Th17/Treg失衡可能在动脉粥样硬化的形成和进展中发挥作用。2009爱思唯尔有限公司版权所有。
Objective: Atherosclerosis is a chronic inflammatory disease regulated by T lymphocyte subsets. Recently, CD4(+) CD25(+) Foxp3(+) regulatory T (Treg) cells and Th17 cells have been described as two distinct subsets and have the opposite effects on autoimmunity. Clinical observation has revealed that the Th17/Treg imbalance exists in patients with acute coronary syndrome. We investigated whether the Th17/Treg functional imbalance existed during atherogenesis in ApoE(-/-) mice. Methods and results: Th17/Treg functions at different levels including cell frequencies, related cytokine secretion and key transcription factors were investigated comparatively between ApoE(-/-) mice and their age-matched C57BL/6J mice. The results demonstrated that ApoE(-/-) mice revealed significantly increased secretion of Th17 related cytokines (IL-17 and IL-6) and expression of transcription factor (ROR gamma t) levels and obviously decreased number in Treg cells, secretion of Treg related cytokines (TGF-beta(1)) and expression of transcription factor (Foxp3) levels as compared with age-matched C57BL/6J mice. Th17 related mediators reached their maximum expression values at the early stage (8-16 weeks of age) in ApoE(-/-) mice, and then followed by continuous depression of their expression levels. Meanwhile, the expression of Treg related mediators was much lower in ApoE(-/-) mice than in their age-matched wild-type littermates. Conclusions: Th17/Treg functional imbalance exists during atherogenesis in ApoE(-/-) mice, suggesting a potential role of Th17/Treg imbalance in the formation and progression of atherosclerosis. (C) 2009 Elsevier Ltd. All rights reserved.