CCL17-expressing dendritic cells drive atherosclerosis by restraining regulatory T cell homeostasis in mice

被引：222

作者：

Weber, Christian ^{[1
,2
,3
]}

Meiler, Svenja ^{[3
,4
]}

Doering, Yvonne ^{[1
,6
]}

Koch, Miriam ^{[4
]}

Drechsler, Maik ^{[3
,4
]}

Megens, Remco T. A. ^{[1
,3
,7
]}

Rowinska, Zuzanna ^{[3
,5
]}

Bidzhekov, Kiril ^{[1
,3
]}

Fecher, Caroline ^{[4
]}

Ribechini, Eliana ^{[8
]}

van Zandvoort, Marc A. M. J. ^{[2
,3
]}

Binder, Christoph J. ^{[9
,10
]}

Jelinek, Ivett ^{[6
]}

Hristov, Mihail ^{[1
,3
]}

Boon, Louis ^{[11
]}

Jung, Steffen ^{[12
]}

Korn, Thomas ^{[13
]}

Lutz, Manfred B. ^{[8
]}

Foerster, Irmgard ^{[14
]}

Zenke, Martin ^{[6
]}

Hieronymus, Thomas ^{[6
]}

Junt, Tobias ^{[15
]}

Zernecke, Alma ^{[2
,4
]}

机构：

[1] Univ Munich, Inst Cardiovasc Prevent, D-80336 Munich, Germany

[2] Maastricht Univ, Cardiovasc Res Inst Maastricht CARIM, Maastricht, Netherlands

[3] Rhein Westfal TH Aachen, Fac Med, Inst Mol Cardiovasc Res IMCAR, Aachen, Germany

[4] Univ Wurzburg, Rudolf Virchow Zentrum, DFG Res Ctr Expt Med, D-97080 Wurzburg, Germany

[5] Rhein Westfal TH Aachen, Univ Hosp, European Vasc Ctr Aachen Maastricht, Aachen, Germany

[6] Rhein Westfal TH Aachen, Dept Cell Biol, Inst Biomed Engn, Aachen, Germany

[7] Rhein Westfal TH Aachen, Interdisciplinary Ctr Clin Res, Aachen, Germany

[8] Univ Wurzburg, Inst Virol & Immunbiol, D-97080 Wurzburg, Germany

[9] Med Univ Vienna, Dept Lab Med, Vienna, Austria

[10] Med Univ Vienna, Austrian Acad Sci, Ctr Mol Med CeMM, Vienna, Austria

[11] Bioceros BV, Utrecht, Netherlands

[12] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel

[13] Tech Univ Munich, Klinikum Rechts Isar, Dept Neurol, D-8000 Munich, Germany

[14] IUF Leibniz Res Inst Environm Med, Dusseldorf, Germany

[15] Novartis Pharma AG, Basel, Switzerland

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2011年 / 121卷 / 07期

关键词：

MACROPHAGE-DERIVED CHEMOKINE; LOW-DENSITY-LIPOPROTEIN; DEFICIENT MICE; IN-VIVO; ARTERIAL INTIMA; STEADY-STATE; ACTIVATION; RECEPTORS; INFLAMMATION; EXPRESSION;

D O I：

10.1172/JCI44925

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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.

引用

页码：2898 / 2910

页数：13

共 70 条

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