Leukocyte Bim deficiency does not impact atherogenesis in ldlr -/- mice, despite a pronounced induction of autoimmune inflammation
| Autor: | Niek van Bree, Ilze Bot, Bart J.M. van Vlijmen, Tom G. Keulers, Marijke M. Westra, Thomas G. Cotter, Theo J.C. Van Berkel, Erik A.L. Biessen, Lieve Temmerman, Kim L. L. Habets, Johan van der Vlag, Martine Bot |
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| Přispěvatelé: | RS: CARIM - R3.06 - The vulnerable plaque: makers and markers, Radiotherapie, Promovendi ODB, RS: GROW - R2 - Basic and Translational Cancer Biology, Pathologie |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
BCL-2 FAMILY OXIDIZED LDL Science LOW-DENSITY-LIPOPROTEIN Autoimmunity chemical and pharmacologic phenomena IMMUNITY medicine.disease_cause DENDRITIC CELLS 03 medical and health sciences medicine HUMAN ATHEROSCLEROTIC PLAQUES Macrophage T-CELL DEATH TRANSGENIC MICE Autoimmune disease Multidisciplinary Interferon-gamma production business.industry Bcl-2 family hemic and immune systems Chronic inflammation Atherosclerosis medicine.disease 3. Good health Experimental models of disease Haematopoiesis 030104 developmental biology medicine.anatomical_structure Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11] FAMILY-MEMBER BIM B-CELLS Immunology ddc:000 Medicine Bone marrow biological phenomena cell phenomena and immunity business CD8 |
| Zdroj: | Scientific Reports, 7 Scientific Reports Scientific Reports, 7, 3086 Scientific Reports, Vol 7, Iss 1, Pp 1-11 (2017) Scientific reports 7, 3086 (2017). doi:10.1038/s41598-017-02771-4 Scientific Reports, 7:3086. Nature Publishing Group |
| ISSN: | 2045-2322 |
| Popis: | Proapoptotic Bcl-2 family member Bim is particularly relevant for deletion of autoreactive and activated T and B cells, implicating Bim in autoimmunity. As atherosclerosis is a chronic inflammatory process with features of autoimmune disease, we investigated the impact of hematopoietic Bim deficiency on plaque formation and parameters of plaque stability. Bim−/− or wild type bone marrow transplanted ldlr−/− mice were fed a Western type diet (WTD) for 5 or 10 weeks, after which they were immunophenotyped and atherosclerotic lesions were analyzed. Bim−/− transplanted mice displayed splenomegaly and overt lymphocytosis. CD4+ and CD8+ T cells were more activated (increased CD69 and CD71 expression, increased interferon gamma production). B cells were elevated by 147%, with a shift towards the pro-atherogenic IgG-producing B2 cell phenotype, resulting in a doubling of anti-oxLDL IgG1 antibody titers in serum of bim−/− mice. Bim−/− mice displayed massive intraplaque accumulation of Ig complexes and of lesional T cells, although this did not translate in changes in plaque size or stability features (apoptotic cell and macrophage content). The surprising lack in plaque phenotype despite the profound pro-atherogenic immune effects may be attributable to the sharp reduction of serum cholesterol levels in WTD fed bim−/− mice. |
| Databáze: | OpenAIRE |
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