title: Genetic deletion of chemokine receptor Ccr6 decreases atherogenesis in ApoE-deficient mice.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Wuzhou
authors.initials: W
authors.lastname: Wan
authors.forename: Jean K
authors.initials: JK
authors.lastname: Lim
authors.forename: Michail S
authors.initials: MS
authors.lastname: Lionakis
authors.forename: Aymeric
authors.initials: A
authors.lastname: Rivollier
authors.forename: David H
authors.initials: DH
authors.lastname: McDermott
authors.forename: Brian L
authors.initials: BL
authors.lastname: Kelsall
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Farber
authors.forename: Philip M
authors.initials: PM
authors.lastname: Murphy
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000097:blood; D001011:Aorta / Q000276:immunology* / Q000473:pathology; D001018:Aortic Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D016026:Bone Marrow Transplantation; D039481:CD11b Antigen / Q000097:blood; D002460:Cell Line; D054418:Chemokine CCL20 / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D004195:Disease Models, Animal; D005260:Female; D017353:Gene Deletion; D007958:Leukocyte Count; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology; D054399:Receptors, CCR6 / Q000172:deficiency* / Q000235:genetics; D013997:Time Factors
chemical_list: D000950:Antigens, Ly; D001057:Apolipoproteins E; C493447:CCL20 protein, mouse; C498126:CCR6 protein, mouse; D039481:CD11b Antigen; D054418:Chemokine CCL20; C494192:Ly-6C antigen, mouse; D054399:Receptors, CCR6