CX3CR1 deficiency impairs the recruitment of dendritic cells to the arterial intima and reduces atherosclerotic burden (98.7)

Abstract

Abstract Dendritic cells (DCs) have recently been found in atherosclerosis-predisposed regions of arteries and have been proposed to be causal in atherosclerosis. Our previous studies demonstrated that the chemokine receptor CX3CR1 is associated with arterial injury and atherosclerosis. Here we investigated if DC arterial accumulation was correlated with atherosclerosis and the mechanisms by which CX3CR1 may play a role. 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 curvature. Consistent with the increased accumulation of intimal DCs in aging (2196.2±154) and ApoE−/−aortas (2697.5±214.3) compared to young WT aortas (904±79.5, p=0.004 and 0.05 respectively), the incidence of atherosclerosis was 88.9% for aging and 100% for ApoE−/− mice. CX3CR1 was expressed on intimal DCs, and DC numbers were decreased in CX3CR1−/− aortas (541.1±93.6 vs. 904±79.5 for WT, p=0.0008). CX3CR1-deficiency decreased atherosclerosis in aortas of ApoE−/−mice by 71% (0.41%±0.11% of aorta surface for ApoE−/−/CX3CR1−/− vs. 1.39%±0.02% for ApoE−/−, p=0.00006). Thus, the accumulation of intimal DC increases in aging and ApoE−/− aortas and correlates with the generation of atherosclerosis. CX3CR1-deficiency impairs the recruitment of DC to the aortic wall and markedly reduces the atherosclerotic burden.