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.
Christian Weber, Svenja Meiler, Yvonne Döring, Miriam Koch, Maik Drechsler, Remco T.A. Megens, Zuzanna Rowinska, Kiril Bidzhekov, Caroline Fecher, Eliana Ribechini, Marc A.M.J. van Zandvoort, Christoph J. Binder, Ivett Jelinek, Mihail Hristov, Louis Boon, Steffen Jung, Thomas Korn, Manfred B. Lutz, Irmgard Förster, Martin Zenke, Thomas Hieronymus, Tobias Junt, Alma Zernecke
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