Thymic stromal lymphopoietin attenuates the development of atherosclerosis in ApoE-/- mice.
Thymic stromal lymphopoietin attenuates the development of atherosclerosis in ApoE-/- mice.
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胸腺基质淋巴细胞生成素可减轻 ApoE-/- 小鼠动脉粥样硬化的发展。
DOI：
10.1161/jaha.113.000391
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发表时间：
2013-08-28
影响因子：
5.4
通讯作者：
Zeng Q
中科院分区：
文献类型：
--
作者：
Yu K;Zhu P;Dong Q;Zhong Y;Zhu Z;Lin Y;Huang Y;Meng K;Ji Q;Yi G;Zhang W;Wu B;Mao Y;Cheng P;Zhao X;Mao X;Zeng Q
胸腺基质淋巴细胞生成素（TSLP）是一种对身体具有多种作用的细胞因子。一方面，TSLP 诱导 Th2 免疫反应并促进过敏反应；另一方面，它促进天然存在的 CD4+CD25+Foxp3+ 调节性 T 细胞 (nTreg) 的分化并维持免疫耐受。然而，TSLP 在动脉粥样硬化中的确切作用仍不清楚。在体外，我们检查了载脂蛋白 E 缺陷 (ApoE−/−) 小鼠的 TSLP 条件骨髓树突状细胞 (TSLP-DC) 的表型及其诱导 Tregs 分化的能力。我们的结果表明，TSLP-DCs 获得了耐受性树突状细胞的特征，并在与初始 T 细胞共培养时增加了 CD4+ 潜伏相关肽 (LAP)+ Tregs 和 nTregs 的生成。此外，还确定了 TSLP 和 TSLP-DC 在动脉粥样硬化发展中的功能相关性。有趣的是，我们发现ApoE−/−小鼠的心血管组织中几乎不存在TSLP，并且TSLP给药增加了血浆中抗氧化低密度脂蛋白IgM和IgG1的水平，但降低了IgG2a的水平。此外，与对照组相比，接受 TSLP 和 TSLP-DC 治疗的小鼠主动脉根部动脉粥样硬化斑块明显减少（分别为 32.6% 和 28.2%），脾脏中 CD4+LAP+ Tregs 和 nTreg 数量增加，主动脉炎症减少，而抗 TGF-β 抗体可以消除这些炎症。我们的结果揭示了 TSLP 在动脉粥样硬化中的保护作用，这可能是通过重建耐受性免疫反应介导的，这可能代表了治疗或预防动脉粥样硬化的新可能性。
Thymic stromal lymphopoietin (TSLP) is a cytokine with multiple effects on the body. For one thing, TSLP induces Th2 immunoreaction and facilitates allergic reaction; for another, it promotes the differentiation of naturally occurring CD4+CD25+Foxp3+ regulatory T cells (nTregs) and maintains immune tolerance. However, the exact role of TSLP in atherosclerosis remains unknown. In vitro, we examined the phenotype of TSLP‐conditioned bone marrow dendritic cells (TSLP‐DCs) of apolipoprotein E–deficient (ApoE−/−) mice and their capacity to induce the differentiation of Tregs. Our results indicated that TSLP‐DCs obtained the characteristics of tolerogenic dendritic cells and increased a generation of CD4+ latency‐associated peptide (LAP)+ Tregs and nTregs when cocultured with naive T cells. In addition, the functional relevance of TSLP and TSLP‐DCs in the development of atherosclerosis was also determined. Interestingly, we found that TSLP was almost absent in cardiovascular tissue of ApoE−/− mice, and TSLP administration increased the levels of antioxidized low‐density lipoprotein IgM and IgG1, but decreased the levels of IgG2a in plasma. Furthermore, mice treated with TSLP and TSLP‐DCs developed significantly fewer (32.6% and 28.2%, respectively) atherosclerotic plaques in the aortic root compared with controls, along with increased numbers of CD4+LAP+ Tregs and nTregs in the spleen and decreased inflammation in the aorta, which could be abrogated by anti‐TGF‐β antibody. Our results revealed a protective role for TSLP in atherosclerosis that is possibly mediated by reestablishing a tolerogenic immune response, which may represent a novel possibility for treatment or prevention of atherosclerosis.