Journal
THROMBOSIS AND HAEMOSTASIS
Volume 110, Issue 6, Pages 1267-1277Publisher
SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN
DOI: 10.1160/TH13-01-0017
Keywords
Atherosclerosis; chemokines; CCR6; monocyte; recruitment
Categories
Funding
- Deutsche Forschungsgemeinschaft [Hu1618/1-2, SF8688 TP A12, ZE 827/1-2, ZE 827/4-1]
- ZonMW [VIDI 016.126358]
Ask authors/readers for more resources
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(-1-)) mice were crossed with low-density lipoprotein receptor-deficient (Ldlrl(-/-)) mice to generate atherosclerosis-prone mice deficient in CCR6. Compared to Ldl(-/-) controls, atherosclerotic burden in the aortic sinus and aorta were reduced in Ccr6(-1-)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(-1-)Ldrlr(-/-) 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available