CCR6 selectively promotes monocyte mediated inflammation and atherogenesis in mice.
THROMBOSIS AND HAEMOSTASIS(2013)
摘要
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.
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关键词
Atherosclerosis,chemokines,CCR6,monocyte,recruitment
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