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Atherosclerosis still is the major cause of death in developed countries. It is considered to be an inflammatory disease with different immune cells contributing to atherogenesis.
Previously, it has been demonstrated that T-cell interactions with antigen presenting cells (APC) contribute to chronic inflammation in atherosclerosis. The exact mechanisms, how APC modulate atheroprogression, however, are incompletely characterized.
Using a LacZ reporter mouse, we observed that CD11c positive cells are enriched in the aortic arch of ApoE -/- mice fed a high cholesterol diet.
Systemic long-term depletion of CD11c positive cells after transfer of bone marrow of CD11c-GFP-diphteria toxin receptor (CD11c-DTR) mice into ApoE -/- mice by injection of diphtheria toxin resulted in significantly increased plaque formation in the aorta as demonstrated by oil red staining, whereas diphtheria toxin treatment without bone marrow transfer had no effect on plaque formation. Interestingly, we measured increased amounts of ApoE in the supernatant of bone marrow derived dendritic cells (DCs) upon stimulation with acetylated LDL (acLDL), and we observed reduced serum levels of ApoE in ApoE -/- mice reconstituted with CD11c-DTR bone marrow after depletion of CD11c positive cells compared to control treated animals. In conclusion, or data indicates that CD11c positive cells ameliorate atherosclerosis in ApoE -/- mice potentially by the secretion of ApoE and we will further investigate the underlying mechanisms.
