Institute for Cardiovascular Prevention, Ludwig-Maximilians-Universität München, Munich, Germany.
J Clin Invest. 2011 Jul;121(7):2898-910. doi: 10.1172/JCI44925.
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.
免疫机制被认为可以控制动脉粥样硬化的发病机制。然而，对于树突状细胞（DC）在免疫反应中的作用仍然难以确定。我们在这里表明，趋化因子 CCL17 在人类和鼠的动脉粥样硬化的晚期存在，并且 CCL17+ DC 聚集在动脉粥样硬化病变中。在易患动脉粥样硬化的小鼠中，Ccl17 缺陷导致动脉粥样硬化减少，这依赖于 Tregs。DC 表达 CCL17 通过限制其维持来限制 Tregs 的扩增，并通过 T 细胞介导的机制引发动脉粥样硬化。相反，针对 CCL17 的阻断抗体特异性地扩增了 Tregs，并减少了动脉粥样硬化进展。我们的数据确定了 DC 衍生的 CCL17 是 Treg 稳态的中心调节剂，提示 DC 及其效应功能参与了动脉粥样硬化的发生，并表明 CCL17 可能是血管治疗的靶点。
