In:
Thrombosis and Haemostasis, Georg Thieme Verlag KG, Vol. 110, No. 12 ( 2013), p. 1267-1277
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-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.
Type of Medium:
Online Resource
ISSN:
0340-6245
,
2567-689X
DOI:
10.1160/TH13-01-0017
Language:
English
Publisher:
Georg Thieme Verlag KG
Publication Date:
2013
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