TY - JOUR
T1 - CCL17-expressing dendritic cells drive atherosclerosis by restraining regulatory T cell homeostasis in mice
AU - Weber, Christian
AU - Meiler, Svenja
AU - Döring, Yvonne
AU - Koch, Miriam
AU - Drechsler, Maik
AU - Megens, Remco T.A.
AU - Rowinska, Zuzanna
AU - Bidzhekov, Kiril
AU - Fecher, Caroline
AU - Ribechini, Eliana
AU - Van Zandvoort, Marc A.M.J.
AU - Binder, Christoph J.
AU - Jelinek, Ivett
AU - Hristov, Mihail
AU - Boon, Louis
AU - Jung, Steffen
AU - Korn, Thomas
AU - Lutz, Manfred B.
AU - Förster, Irmgard
AU - Zenke, Martin
AU - Hieronymus, Thomas
AU - Junt, Tobias
AU - Zernecke, Alma
PY - 2011/7
Y1 - 2011/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79960020852&partnerID=8YFLogxK
U2 - 10.1172/JCI44925
DO - 10.1172/JCI44925
M3 - Article
C2 - 21633167
AN - SCOPUS:79960020852
SN - 0021-9738
VL - 121
SP - 2898
EP - 2910
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 7
ER -