Ablation of CD8?(+) dendritic cell mediated cross-presentation does not impact atherosclerosis in hyperlipidemic mice
Legein B, Janssen EM, Theelen TL, Gijbels MJ, Walraven J, Klarquist JS, Hennies CM, Wouters K, Seijkens TTP, Wijnands E, Sluimer JC, Lutgens E, Zenke M, Hildner K, Biessen EAL, Temmerman L (2015)
Publication Type: Journal article
Publication year: 2015
Journal
Book Volume: 5
Pages Range: 15414
DOI: 10.1038/srep15414
Abstract
Clinical complications of atherosclerosis are almost exclusively linked to destabilization of the atherosclerotic plaque. Batf3-dependent dendritic cells specialize in cross-presentation of necrotic tissue-derived epitopes to directly activate cytolytic CD8 Tcells. The mature plaque (necrotic, containing dendritic cells and CD8 Tcells) could offer the ideal environment for cross-presentation, resulting in cytotoxic immunity and plaque destabilization. Ldlr(-/-) mice were transplanted with batf3(-/-) or wt bone marrow and put on a western type diet. Hematopoietic batf3 deficiency sharply decreased CD8?(+) DC numbers in spleen and lymph nodes (>80%; P < 0,001). Concordantly, batf3(-/-) chimeras had a 75% reduction in OT-I cross-priming capacity in vivo. Batf3(-/-) chimeric mice did not show lower Tcell or other leukocyte subset numbers. Despite dampened cross-presentation capacity, batf3(-/-) chimeras had equal atherosclerosis burden in aortic arch and root. Likewise, batf3(-/-) chimeras and wt mice revealed no differences in parameters of plaque stability: plaque Tcell infiltration, cell death, collagen composition, and macrophage and vascular smooth muscle cell content were unchanged. These results show that CD8?(+) DC loss in hyperlipidemic mice profoundly reduces cross-priming ability, nevertheless it does not influence lesion development. Taken together, we clearly demonstrate that CD8?(+) DC-mediated cross-presentation does not significantly contribute to atherosclerotic plaque formation and stability.
Authors with CRIS profile
Involved external institutions
Maastricht University
Netherlands (NL)
Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen
Germany (DE)
University of Amsterdam
Netherlands (NL)
Cincinnati Children's Hospital Medical Center
United States (USA) (US)
Netherlands (NL)
Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen
Germany (DE)
University of Amsterdam
Netherlands (NL)
Cincinnati Children's Hospital Medical Center
United States (USA) (US)
How to cite
APA:
Legein, B., Janssen, E.M., Theelen, T.L., Gijbels, M.J., Walraven, J., Klarquist, J.S.,... Temmerman, L. (2015). Ablation of CD8?(+) dendritic cell mediated cross-presentation does not impact atherosclerosis in hyperlipidemic mice. Scientific Reports, 5, 15414. https://doi.org/10.1038/srep15414
MLA:
Legein, Bart, et al. "Ablation of CD8?(+) dendritic cell mediated cross-presentation does not impact atherosclerosis in hyperlipidemic mice." Scientific Reports 5 (2015): 15414.
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