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

Abstract

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 (Ldlr −/−) mice, CD11c+ MHCII+ DCs could be discriminated into CD103− CD11b+F4/80+, CD11b+F4/80− and CD11b−F4/80− DCs and CD103+ CD11b−F4/80− DCs. Except for CD103− CD11b− F4/80− DCs, these subsets expanded in high fat diet-fed Ldlr −/− mice. Signal-regulatory protein (Sirp)-α was detected on aortic macrophages, CD11b+ DCs, and partially on CD103− CD11b− F4/80− but not on CD103+ DCs. Notably, in FMS-like tyrosine kinase 3-ligand-deficient (Flt3l −/−) mice, a specific loss of CD103+ DCs but also CD103− CD11b+ F4/80− DCs was evidenced. Aortic CD103+ and CD11b+ F4/80− CD103− 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 CD103− CD11b+ F4/80− and CD11b+ F4/80+ cells in atherosclerotic Ldlr −/− mice. The emergence of CD64 expression in atherosclerosis may indicate that CD11b+ F4/80− DCs similar to CD11b+ F4/80+ DCs are at least in part derived from immigrated monocytes during atherosclerotic lesion formation. Our data advance our knowledge about the presence of distinct DC subsets and their accumulation characteristics in atherosclerosis, and may help to assist in future studies aiming at specific DC-based therapeutic strategies for the treatment of chronic vascular inflammation.

Dendritic Cells in Atherosclerosis

“…The loss of CD103 + and of some CD11b + cDCs in the nonatherosclerotic aorta in Flt3/Flt3l-deficient mice 4,14 indicates that monocyte-derived DCs and bone fide cDCs are already present prior disease development. Whereas blood monocytes systemically increase, 34 it is unclear whether circulating DCs or their precursors are altered in hyperlipidemia.…”

Deletion of Batf3-dependent antigen-presenting cells does not affect atherosclerotic lesion formation in mice

“…No differences in pDCs were noted (0.37% ± 0.08% versus 0.32% ± 0.03% CD11c low/+ Siglec H + cells among CD45 + cellls in Ldlr -/- versus Ldlr -/- Batf3 -/- mice, respectively). CD103 + DCs can be found within the aortic sinus of chow-fed animals where they represent up to 20% of total DCs [ 14 , 23 ]. As expected, CD103 + APC were completely absent in cell suspensions prepared from the aortic sinus of Ldlr -/- Batf3 -/- mice compared to control Ldlr -/- animals, whereas a relative increase in CD11b + APCs were observed (Panel C in S1 Fig ).…”

“…in the intestinal mucosa [ 29 , 30 ]. However, Flt3 is not only expressed in this DC subset but is also present in other CD11c + MHCII + DC subsets, and we have previously shown that deficiency in its ligand in Flt3 -/- mice for example resulted not only in a loss of CD103 + DCs in the aorta, but in addition was associated with a marked reduction in CD11b + DCs [ 23 ]. Flt3 can also be found on some natural killer (NKs) cells [ 31 , 32 ].…”

Single‐cell analyses reveal functional classification of dendritic cells and their potential roles in inflammatory disease

“…Previous research revealed that DCs accumulate in atherosclerotic lesions (38) and are predisposed to atherosclerosis, which is a well-known, chronic inflammatory disease of the large and medium arteries (39). We then concentrated on the migration ability of DCs in ApoE 2/2 mice and demonstrated an unexpected change in DCs, which could be hidden by traditional bulk-cell analysis.…”