CX3CR1 deficiency impairs dendritic cell accumulation in arterial intima and reduces atherosclerotic burden.
OBJECTIVE
Dendritic cells (DCs) have recently been found in atherosclerosis-predisposed regions of arteries and have been proposed to be causal in atherosclerosis. The chemokine receptor CX3CR1 is associated with arterial injury and atherosclerosis. We sought to determine whether a link exists between arterial DC accumulation, CX3CR1, and atherosclerosis.


RESULTS
Mouse aortas were isolated and subjected to en face immunofluorescence analysis. We found that DCs were located predominantly in the intimal regions of arterial branch points and curvatures. Consistent with the increased accumulation of intimal DCs in aged and ApoE-/- aortas compared with young WT aortas (P=0.004 and 0.05, respectively), the incidence of atherosclerosis was 88.9% for aged WT and 100% for ApoE-/- mice compared with 0% for young WT mice. CX3CR1 was expressed on intimal DCs and DC numbers were decreased in CX3CR1-deficient aortas of young, aged, and ApoE-/- mice (P=0.0008, 0.013, and 0.0099). The reduced DC accumulation in CX3CR1-deficiency was also correlated with decreased atherosclerosis in these animals.


CONCLUSIONS
The accumulation of intimal DC increases in aged and ApoE-/- aortas and correlates with the generation of atherosclerosis. CX3CR1-deficiency impairs the accumulation of DC in the aortic wall and markedly reduces the atherosclerotic burden.
Liu
Peng
P
Thurston Arthritis Research Center and Department of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599-7280, USA.
Yu
Yen-Rei A
YR
Spencer
Jessica A
JA
Johnson
Ashley E
AE
Vallanat
Christopher T
CT
Fong
Alan M
AM
Patterson
Cam
C
Patel
Dhavalkumar D
DD
D000375:Aging / Q000502:physiology; D000818:Animals; D001011:Aorta / Q000503:physiopathology*; D001057:Apolipoproteins E / Q000235:genetics / Q000502:physiology; D050197:Atherosclerosis / Q000378:metabolism / Q000503:physiopathology*; D000073883:CX3C Chemokine Receptor 1; D003713:Dendritic Cells / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D019707:Receptors, Chemokine / Q000235:genetics / Q000502:physiology*; D017539:Tunica Intima / Q000378:metabolism / Q000503:physiopathology*
D001057:Apolipoproteins E; D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; D019707:Receptors, Chemokine