Dendritic Cell Subset Distributions in the Aorta in Healthy and Atherosclerotic Mice

Dendritic cells (DCs) can be sub-divided into various subsets that play specialized roles in priming of adaptive immune responses. Atherosclerosis is regarded as a chronic inflammatory disease of the vessel wall and DCs can be found in non-inflamed and diseased arteries. We here performed a systematic analyses of DCs subsets during atherogenesis. Our data indicate that distinct DC subsets can be localized in the vessel wall. In C57BL/6 and low density lipoprotein receptor-deficient (Ldlr2/2) mice, CD11c+ MHCII+ DCs could be discriminated into CD1032 CD11b+F4/80+, CD11b+F4/802 and CD11b2F4/802 DCs and CD103+ CD11b2F4/802 DCs. Except for CD1032 CD11b2 F4/802 DCs, these subsets expanded in high fat diet-fed Ldlr2/2 mice. Signal-regulatory protein (Sirp)-a was detected on aortic macrophages, CD11b+ DCs, and partially on CD1032 CD11b2 F4/802 but not on CD103+ DCs. Notably, in FMS-like tyrosine kinase 3-ligand-deficient (Flt3l2/ 2) mice, a specific loss of CD103+ DCs but also CD1032 CD11b+ F4/802 DCs was evidenced. Aortic CD103+ and CD11b+ F4/ 802 CD1032 DCs may thus belong to conventional rather than monocyte-derived DCs, given their dependence on Flt3L-signalling. CD64, postulated to distinguish macrophages from DCs, could not be detected on DC subsets under physiological conditions, but appeared in a fraction of CD1032 CD11b+ F4/802 and CD11b+ F4/80+ cells in atherosclerotic Ldlr2/2mice. The emergence of CD64 expression in atherosclerosis may indicate that CD11b+ F4/802 DCs similar to CD11b+ F4/80+ DCs are at least in part derived from immigrated monocytes during atherosclerotic lesion formation. Our dat