TY  - JOUR
A1  - Busch, Martin
A1  - Westhofen, Thilo C.
A1  - Koch, Miriam
A1  - Lutz, Manfred B.
A1  - Zernecke, Alma
T1  - Dendritic Cell Subset Distributions in the Aorta in Healthy and Atherosclerotic Mice
JF  - PLoS ONE
N2  - 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.
KW  - flow cytometry
KW  - monocytes
KW  - diet
KW  - cell staining
KW  - DAPI staining
KW  - aorta
KW  - macrophages
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-119907
SN  - 1932-6203
VL  - 9
IS  - 2
ER  - 
TY  - JOUR
A1  - Cochain, Clement
A1  - Chaudhari, Sweena M.
A1  - Koch, Miriam
A1  - Wiendl, Heinz
A1  - Eckstein, Hans-Henning
A1  - Zernecke, Alma
T1  - Programmed Cell Death-1 Deficiency Exacerbates T Cell Activation and Atherogenesis despite Expansion of Regulatory T Cells in Atherosclerosis-Prone Mice
JF  - PLoS ONE
N2  - T cell activation represents a double-edged sword in atherogenesis, as it promotes both pro-inflammatory T cell activation and atheroprotective Foxp3(+) regulatory T cell (Treg) responses. Here, we investigated the role of the co-inhibitory receptor programmed cell death-1 (PD-1) in T cell activation and CD4(+) T cell polarization towards pro-atherogenic or atheroprotective responses in mice. Mice deficient for both low density lipoprotein receptor and PD-1 (Ldlr(-/-)Pd1(-/-)) displayed striking increases in systemic CD4(+) and CD8(+) T cell activation after 9 weeks of high fat diet feeding, associated with an expansion of both pro-atherogenic IFNγ-secreting T helper 1 cells and atheroprotective Foxp3+ Tregs. Importantly, PD-1 deficiency did not affect Treg suppressive function in vitro. Notably, PD-1 deficiency exacerbated atherosclerotic lesion growth and entailed a massive infiltration of T cells in atherosclerotic lesions. In addition, aggravated hypercholesterolemia was observed in Ldlr(-/-)Pd1(-/-) mice. In conclusion, we here demonstrate that although disruption of PD-1 signaling enhances both pro- and anti-atherogenic T cell responses in Ldlr(-/-) mice, pro-inflammatory T cell activation prevails and enhances dyslipidemia, vascular inflammation and atherosclerosis.
KW  - nutritional deficiencies
KW  - atherosclerosis
KW  - spleen
KW  - aorta
KW  - diet
KW  - cytotoxic T cells
KW  - regulatory T cells
KW  - T cells
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-119823
SN  - 1932-6203
VL  - 9
IS  - 4
ER  -