Changes in CD4+CD25+ Tregs in the pathogenesis of atherosclerosis in ApoE-/- mice
Changes in CD4+CD25+ Tregs in the pathogenesis of atherosclerosis in ApoE-/- mice
复制标题
ApoE/小鼠动脉粥样硬化发病机制中 CD4+CD25+Treg 的变化
DOI：
10.1177/1535370216689826
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发表时间：
2017-05-01
影响因子：
3.2
通讯作者：
Li Yu-Jie
中科院分区：
文献类型：
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作者：
Li Xue-Mei;Chen Jie;Li Yu-Jie
本研究旨在观察ApoE(-/-)和C57BL/6J小鼠主动脉壁动脉粥样硬化斑块的病理特征以及动脉粥样硬化小鼠体内CD4(+)CD25(+)调节性T细胞(Treg)的变化。将20只ApoE(-/-)小鼠分为高脂饮食(AH)组和正常饮食(AN)组，并将10只C57BL/6J雄性小鼠指定为对照组(BN)。采用酶联免疫吸附法检测血清IL-10、TGF-β1浓度；主动脉石蜡切片用苏木精和伊红染色，并使用 Image Pro Plus 6.0 系统测量形态参数。 Verhoeff染色观察弹力纤维分布情况，免疫组化染色验证动脉粥样硬化组织中叉头盒蛋白3（Foxp3（+））CD25（+）细胞的表型。通过流式细胞仪计算脾脏中CD4(+)CD25(+) Tregs的比例。 AN组小鼠内膜厚度、内膜/中膜比、斑块面积、斑块/管腔比均显着大于BN组小鼠。 AH组小鼠的内膜厚度、斑块面积、斑块/管腔比均较AN组小鼠显着增加。 AN组小鼠血清IL-10、TGF-β1浓度及脾脏CD4(+)CD25(+) Tregs比例较对照组显着降低。与AN组相比，AH组小鼠血清IL-10、TGF-β1浓度以及脾脏CD4(+)CD25(+) Tregs百分比均显着降低。与AN组小鼠相比，AH组小鼠淋巴细胞总数中Foxp3(+)和CD25(+)细胞的比例显着降低。实验小鼠模型中的动脉粥样硬化与淋巴组织和斑块中的 Treg 耗竭相关，表明 CD4(+)CD25(+) Tregs 具有重要的抗动脉粥样硬化作用。
The goal of this study was to observe the pathological characteristics of atherosclerotic plaques in the aortic walls of ApoE(-/-) and C57BL/6J mice and the changes of CD4(+)CD25(+) regulatory T cells (Tregs) in atherosclerotic mice. Twenty ApoE(-/-) mice were split into high-fat diet (AH) and normal diet (AN) groups and 10 C57BL/6J male mice were designated as the control group (BN). The serum concentrations of IL-10 and TGF-beta 1 were detected by enzyme-linked immunosorbent assay; paraffin sections of the aorta were stained with hematoxylin & eosin, and morphometric parameters were measured using the Image Pro Plus 6.0 system. Verhoeff stain was used to observe the distribution of elastic fibers, and immunohistochemical staining was performed to verify the phenotype of the forkhead box protein 3 (Foxp3(+)) CD25(+) cells in the atherosclerotic tissue. The proportion of CD4(+)CD25(+) Tregs in the spleen was calculated by flow cytometry. The thickness of the intima, the intima/media ratio, the plaque area, and the plaque/lumen ratio of mice in AN group were significantly larger than those of mice in BN group. The thickness of the intima, the plaque area, and the plaque/lumen ratio of the mice in AH group were significantly increased compared with those of the AN group mice. The serum concentrations of IL-10 and TGF-beta 1 and the percentage of splenic CD4(+)CD25(+) Tregs in AN group mice were significantly decreased compared with the control group. The serum concentrations of IL-10 and TGF-beta 1 and the percentage of splenic CD4(+)CD25(+) Tregs in the mice in AH group were significantly decreased compared with those in AN group. The proportions of Foxp3(+) and CD25(+) cells within the total lymphocyte population were significantly decreased in AH group mice compared with those in AN group mice. Atherosclerosis in an experimental mouse model was correlated with Treg depletion in the lymphoid tissues and plaques, indicating the important antiatherosclerotic role of CD4(+)CD25(+) Tregs.