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Thromb Haemost 2013; 110(06): 1267-1277
DOI: 10.1160/TH13-01-0017
Platelets and Blood Cells
Schattauer GmbH

CCR6 selectively promotes monocyte mediated inflammation and atherogenesis in mice

Helga D. Manthey   *
1   Rudolf Center for Experimental Medicine, University of Würzburg, Wurzburg, Germany
,
Clément Cochain   *
2   Department of Vascular Surgery, Klinikum rechts der Isar, Technical University Munich, Germany
,
Stefanie Barnsteiner   *
1   Rudolf Center for Experimental Medicine, University of Würzburg, Wurzburg, Germany
,
Ela Karshovska
3   Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich, Munich, Germany
,
Jaroslav Pelisek
2   Department of Vascular Surgery, Klinikum rechts der Isar, Technical University Munich, Germany
,
Miriam Koch
1   Rudolf Center for Experimental Medicine, University of Würzburg, Wurzburg, Germany
,
Sweena M. Chaudhari
1   Rudolf Center for Experimental Medicine, University of Würzburg, Wurzburg, Germany
2   Department of Vascular Surgery, Klinikum rechts der Isar, Technical University Munich, Germany
,
Martin Busch
1   Rudolf Center for Experimental Medicine, University of Würzburg, Wurzburg, Germany
,
Hans-Henning Eckstein
2   Department of Vascular Surgery, Klinikum rechts der Isar, Technical University Munich, Germany
4   DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany
,
Christian Weber
3   Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich, Munich, Germany
4   DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany
,
Rory R. Koenen
3   Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich, Munich, Germany
,
Alma Zernecke
2   Department of Vascular Surgery, Klinikum rechts der Isar, Technical University Munich, Germany
4   DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany
› Author Affiliations Financial support: This work was supported by the Deutsche Forschungsgemeinschaft (Hu1618/1–2 to R.R.K, and SFB688 TP A12, ZE 827/1–2 and ZE 827/4–1 to A.Z.), and ZonMW VIDI 016.126.358 to R.R.K.
Further Information

Publication History

Received: 09 January 2013

Accepted after major revision: 19 August 2013

Publication Date:
30 November 2017 (online)

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Summary

The chemokine receptor CCR6 is expressed by various cell subsets implicated in atherogenesis, such as monocytes, Th17 and regulatory T cells. In order to further define the role of CCR6 in atherosclerosis, CCR6-deficient (Ccr6 -/-) mice were crossed with low-density lipoprotein receptor-deficient (Ldlr -/-) mice to generate atherosclerosis-prone mice deficient in CCR6. Compared to Ldlr -/- controls, atherosclerotic burden in the aortic sinus and aorta were reduced in Ccr6 -/- Ldlr -/- mice fed a high fat diet, associated with a profound depression in lesional macrophage accumulation. Local and systemic distributions of T cells, including frequencies of Th1, Th17 and regulatory T cells were unaltered. In contrast, circulating counts of both Gr-1high and Gr1low monocytes were reduced in Ccr6 -/- Ldlr -/- mice. Moreover, CCR6 was revealed to promote monocyte adhesion to inflamed endothelium in vitro and leukocyte adhesion to carotid arteries in vivo. Finally, CCR6 selectively recruited monocytes but not T cells in an acute inflammatory air pouch model. We here show that CCR6 functions on multiple levels and regulates the mobilisation, adhesion and recruitment of monocytes/macrophages to the inflamed vessel, thereby promoting atherosclerosis, but is dispensable for hypercholesterolaemia-associated adaptive immune priming. Targeting CCR6 or its ligand CCL20 may therefore be a promising therapeutic strategy to alleviate atherosclerosis.

Note: The review process for this manuscript was fully handled by G. Y. H. Lip, Editor in Chief.

Keywords

Atherosclerosis - chemokines - CCR6 - monocyte - recruitment

* Equal contribution by these authors.


 

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