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Circ Res. 2011 Aug 5;109(4):374-81. doi: 10.1161/CIRCRESAHA.111.242578. Epub 2011 Jun 16.

Genetic deletion of chemokine receptor Ccr6 decreases atherogenesis in ApoE-deficient mice.

Author information

  • 1Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Abstract

RATIONALE:

The chemokine receptor Ccr6 is a G-protein-coupled receptor expressed on various types of leukocytes identified in mouse atherosclerotic lesions. Recent evidence suggests that both CCR6 and its ligand CCL20 are also present in human atheroma; however, their functional roles in atherogenesis remain undefined.

OBJECTIVE:

Our objective was to delineate the role of Ccr6 in atherogenesis in the apolipoprotein E-deficient (ApoE(-/-)) mouse model of atherosclerosis.

METHODS AND RESULTS:

Both Ccr6 and Ccl20 are expressed in atherosclerotic aorta from ApoE(-/-) mice. Aortic lesion area in Ccr6(-/-)ApoE(-/-) mice was ∼40% and ∼30% smaller than in Ccr6(+/+)ApoE(-/-) mice at 16 and 24 weeks of age, respectively. Transplantation of bone marrow from Ccr6(-/-) mice into ApoE(-/-) mice resulted in ∼40% less atherosclerotic lesion area than for bone marrow from Ccr6(+/+) mice; lesions in Ccr6(-/-)ApoE(-/-) mice had 44% less macrophage content than lesions in Ccr6(+/+)ApoE(-/-) mice. Ccr6 was expressed on a subset of primary mouse monocytes. Accordingly, Ccl20 induced chemotaxis of primary monocytes from wild-type but not Ccr6(-/-) mice; moreover, Ccl20 induced monocytosis in ApoE(-/-) mice in vivo. Consistent with this, we observed 30% fewer monocytes in circulating blood of Ccr6(-/-)ApoE(-/-) mice, mainly because of fewer CD11b(+)Ly6C(high) inflammatory monocytes.

CONCLUSIONS:

Ccr6 promotes atherosclerosis in ApoE-deficient mice, which may be due in part to Ccr6 support of normal monocyte levels in blood, as well as direct Ccr6-dependent monocyte migration.

PMID:
21680896
[PubMed - indexed for MEDLINE]
PMCID:
PMC3151346
Free PMC Article

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