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.

Methods and 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.