%0 Journal Article
%A Cheng, Fei
%A Twardowski, Laura
%A Reifenberg, Kurt
%A Winter, Kerstin
%A Canisius, Antje
%A Pross, Eva
%A Fan, Jianglin
%A Schmitt, Edgar
%A Shultz, Leonard D
%A Lackner, Karl J
%A Torzewski, Michael
%T Combined B, T and NK Cell Deficiency Accelerates Atherosclerosis in BALB/c Mice.
%J PLoS one
%V 11
%N 8
%@ 1932-6203
%C Lawrence, Kan.
%I PLoS
%M DKFZ-2017-01757
%P e0157311 -
%D 2016
%X This study focused on the unique properties of both the Ldlr knockout defect (closely mimicking the human situation) and the BALB/c (C) inbred mouse strain (Th-2 slanted immune response). We generated two immunodeficient strains with severe combined B- and T-cell immunodeficiency with or without a complete lack of natural killer cells to revisit the role of adaptive immune responses on atherogenesis. C-Ldlr-/- Rag1-/- mice, which show severe combined B- and T-cell immunodeficiency and C-Ldlr-/- Rag1-/- Il2rg-/- mice, which combine the T- and B-cell defect with a complete lack of natural killer cells and inactivation of multiple cytokine signalling pathways were fed an atherogenic Western type diet (WTD). Both B6-Ldlr-/- and C-Ldlr-/- immunocompetent mice were used as controls. Body weights and serum cholesterol levels of both immunodeficient strains were significantly increased compared to C-Ldlr-/- controls, except for cholesterol levels of C-Ldlr-/- Rag1-/- double mutants after 12 weeks on the WTD. Quantification of the aortic sinus plaque area revealed that both strains of immunodeficient mice developed significantly more atherosclerosis compared to C-Ldlr-/- controls after 24 weeks on the WTD. Increased atherosclerotic lesion development in C-Ldlr-/- Rag1-/- Il2rg-/- triple mutants was associated with significantly increased numbers of macrophages and significantly decreased numbers of smooth muscle cells compared to both C-Ldlr-/- wild type and C-Ldlr-/- Rag1-/- double mutants pointing to a plaque destabilizing effect of NK cell loss. Collectively, the present study reveals a previously unappreciated complexity with regard to the impact of lymphocytes on lipoprotein metabolism and the role of lymphocyte subsets in plaque composition.
%K Lipoproteins (NLM Chemicals)
%K Receptors, LDL (NLM Chemicals)
%K Triglycerides (NLM Chemicals)
%K Cholesterol (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:27564380
%2 pmc:PMC5001715
%R 10.1371/journal.pone.0157311
%U https://inrepo02.dkfz.de/record/125631