Genetic Deletion of Chemokine Receptor Ccr6 Decreases Atherogenesis in ApoE-Deficient Mice

Wuzhou Wan, Jean K. Lim, Michail S. Lionakis, Aymeric Marie Christian Rivollier, David H. McDermott, Brian L. Kelsall, Joshua M. Farber, Philip M. Murphy

Research output: Contribution to journalJournal articleResearchpeer-review

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 similar to 40% and similar to 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 similar to 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. (Circ Res. 2011;109:374-381.)
Original languageEnglish
JournalCirculation Research
Volume109
Issue number4
Pages (from-to)374-U91
ISSN0009-7330
DOIs
Publication statusPublished - 2011
Externally publishedYes

Keywords

  • atherosclerosis
  • inflammation
  • monocytes
  • aorta

Fingerprint Dive into the research topics of 'Genetic Deletion of Chemokine Receptor Ccr6 Decreases Atherogenesis in ApoE-Deficient Mice'. Together they form a unique fingerprint.

Cite this