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Thromb Haemost. 2013 Dec;110(6):1267-77. doi: 10.1160/TH13-01-0017. Epub 2013 Oct 10.

CCR6 selectively promotes monocyte mediated inflammation and atherogenesis in mice.

Author information

1
Univ.-Prof. Dr. Alma Zernecke, Klinikum rechts der Isar, Klinik für Gefäßchirurgie, Technische Universität München, Ismaninger Str. 22, 81675 München, Germany, Tel: +49 89 4140 2167, Fax: +49 89 4140 4861, E-mail: zernecke@lrz.tum.de.

Abstract

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-1(high) and Gr1(low) 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.

KEYWORDS:

Atherosclerosis; CCR6; chemokines; monocyte; recruitment

PMID:
24114205
DOI:
10.1160/TH13-01-0017
[Indexed for MEDLINE]
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