Attenuated atherosclerotic lesions in apoE-Fcγ-chain-deficient hyperlipidemic mouse model is associated with inhibition of Th17 cells and promotion of regulatory T cells.
Attenuated atherosclerotic lesions in apoE-Fcγ-chain-deficient hyperlipidemic mouse model is associated with inhibition of Th17 cells and promotion of regulatory T cells.
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DOI：
10.4049/jimmunol.1004133
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发表时间：
2011-12-01
期刊：
影响因子：
--
通讯作者：
Nagarajan S
中科院分区：
文献类型：
--
作者：
Ng HP;Burris RL;Nagarajan S
尽管抗oxLDL IgG的存在在临床和动物研究中得到了充分的证明，但尚未详细研究Fcγ R在动脉粥样硬化进展中的作用。在本研究中，我们使用apoE-Fcγ链双敲除（DKO）小鼠研究了激活FcγR在动脉粥样硬化进展中的作用。相对于apoE KO小鼠，apoE-Fcγ链DKO小鼠的动脉病变形成显著减少。骨髓嵌合体研究显示，接受apoE-Fcγ链DKO小鼠骨髓的apoE KO小鼠的病变减少。与apoE KO小鼠相比，apoE-Fc γ链DKO小鼠中活化T细胞的抗oxLDL IgG 1（Th 2）和IgG 2a（Th 1）、IL-10和IFN-γ分泌增加。这些结果表明，apoE-Fcγ链DKO小鼠动脉粥样硬化病变的减少不是由于Th 1/Th 2失衡。有趣的是，在apoE-Fcγ链DKO小鼠中，Th 17细胞的数量和活化的CD 4+细胞分泌的IL-17减少。值得注意的是，在apoE-Fcγ链DKO小鼠中，T调节细胞的数量、mRNA的表达以及TGF-β和IL-10的分泌增加。此外，在apoE-Fcγ链DKO小鼠中，Th 17细胞生成所必需的IL-6和STAT-3磷酸化的分泌减少。重要的是，apoE-Fcγ链DKO小鼠中Th 17细胞的减少是由于apoE-Fc γ链DKO小鼠的抗原呈递细胞释放的IL-6减少。总之，我们的数据表明，在高脂血症apoE基因敲除小鼠模型中，激活FcγR通过诱导Th 17应答促进动脉粥样硬化。
Though the presence of anti-oxLDL IgG is well documented in clinical and animal studies, the role for FcγRs to the progression of atherosclerosis has not been studied in detail. In the present study, we investigated the role for activating FcγR in the progression of atherosclerosis using apoE-Fcγ chain double knockout (DKO) mice. Relative to apoE KO mice, arterial lesion formation was significantly decreased in apoE-Fcγ chain DKO mice. Bone marrow chimera studies showed reduced lesions in apoE KO mice receiving the bone marrow of apoE-Fcγ chain DKO mice. Compared to apoE KO mice, anti-oxLDL IgG1 (Th2) and IgG2a (Th1), IL-10, and IFN-γ secretion by activated T cells were increased in apoE-Fc γ chain DKO mice. These findings suggest that reduced atherosclerotic lesion in apoE-Fcγ chain DKO mice is not due to Th1/Th2 imbalance. Interestingly, number of Th17 cells and the secretion of IL-17 by activated CD4+ cells were decreased in apoE-Fcγ chain DKO mice. Notably, the number of T-regulatory cells, expression of mRNA, and secretion of TGF-β and IL-10 were increased in apoE-Fcγ chain DKO mice. Furthermore, secretions of IL-6 and STAT-3 phosphorylation essential for Th17 cell genesis were reduced in apoE-Fcγ chain DKO mice. Importantly, decrease in Th17 cells in apoE-Fcγ chain DKO mice was due to reduced IL-6 release by antigen presenting cells of apoE-Fcγ chain DKO mice. Collectively, our data suggest that activating FcγR promotes atherosclerosis by inducing Th17 response in the hyperlipidemic apoE KO mouse model.
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影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
急性冠脉综合征患者Th17/Treg失衡
影响因子：
8.6
作者：
Cheng, Xiang;Yu, Xian;Liao, Yu-hua
通讯作者：
Liao, Yu-hua
影响因子：
4.4
作者：
Erbel, Christian;Chen, Lili;Dengler, Thomas J.
通讯作者：
Dengler, Thomas J.
DOI：
10.1161/01.atv.19.12.2847
发表时间：
1999-12-01
影响因子：
8.7
作者：
Oslund, LJP;Hedrick, CC;Fyfe, AI
通讯作者：
Fyfe, AI
DOI：
10.4049/jimmunol.1001879
发表时间：
2010-11-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Chen S;Shimada K;Zhang W;Huang G;Crother TR;Arditi M
通讯作者：
Arditi M