CCL17-expressing dendritic cells drive atherosclerosis by restraining regulatory T cell homeostasis in mice
CCL17-expressing dendritic cells drive atherosclerosis by restraining regulatory T cell homeostasis in mice
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DOI：
10.1172/jci44925
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发表时间：
2011-07-01
影响因子：
15.9
通讯作者：
Zernecke, Alma
中科院分区：
文献类型：
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作者：
Weber, Christian;Meiler, Svenja;Zernecke, Alma
已知免疫机制控制动脉粥样硬化的发病机制。然而，树突状细胞在启动免疫反应中所起的重要作用仍不清楚。我们已经证明，DC衍生的趋化因子CCL17存在于晚期人类和小鼠动脉粥样硬化中，CCL17(+)DC在动脉粥样硬化病变中积聚。在易患动脉粥样硬化的小鼠中，Ccl17缺乏导致动脉粥样硬化的减轻，这依赖于Tregs。树突状细胞表达CCL17通过限制Tregs的维持而限制其扩张，并通过T细胞赋予的机制加速动脉粥样硬化。相反，针对CCL17的封闭抗体扩大了Tregs并减缓了动脉粥样硬化的进展。我们的数据证实DC来源的CCL17是Treg动态平衡的中央调节因子，涉及DC及其在动脉粥样硬化形成中的效应功能，并提示CCL17可能是血管治疗的靶点。
Immune mechanisms are known to control the pathogenesis of atherosclerosis. However, the exact role of DCs, which are essential for priming of immune responses, remains elusive. We have shown here that the DC-derived chemokine CCL17 is present in advanced human and mouse atherosclerosis and that CCL17(+) DCs accumulate in atherosclerotic lesions. In atherosclerosis-prone mice, Ccl17 deficiency entailed a reduction of atherosclerosis, which was dependent on Tregs. Expression of CCL17 by DCs limited the expansion of Tregs by restricting their maintenance and precipitated atherosclerosis in a mechanism conferred by T cells. Conversely, a blocking antibody specific for CCL17 expanded Tregs and reduced atheroprogression. Our data identify DC-derived CCL17 as a central regulator of Treg homeostasis, implicate DCs and their effector functions in atherogenesis, and suggest that CCL17 might be a target for vascular therapy.