TY  - JOUR
AU  - Cheng, Fei
AU  - Twardowski, Laura
AU  - Reifenberg, Kurt
AU  - Winter, Kerstin
AU  - Canisius, Antje
AU  - Pross, Eva
AU  - Fan, Jianglin
AU  - Schmitt, Edgar
AU  - Shultz, Leonard D
AU  - Lackner, Karl J
AU  - Torzewski, Michael
TI  - Combined B, T and NK Cell Deficiency Accelerates Atherosclerosis in BALB/c Mice.
JO  - PLoS one
VL  - 11
IS  - 8
SN  - 1932-6203
CY  - Lawrence, Kan.
PB  - PLoS
M1  - DKFZ-2017-01757
SP  - e0157311 -
PY  - 2016
AB  - 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.
KW  - Lipoproteins (NLM Chemicals)
KW  - Receptors, LDL (NLM Chemicals)
KW  - Triglycerides (NLM Chemicals)
KW  - Cholesterol (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:27564380
C2  - pmc:PMC5001715
DO  - DOI:10.1371/journal.pone.0157311
UR  - https://inrepo02.dkfz.de/record/125631
ER  -