Leukocyte Bim deficiency does not impact atherogenesis in ldlr −/− mice, despite a pronounced induction of autoimmune inflammation

Abstract 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...

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Autores principales:	Lieve Temmerman, Marijke M. Westra, Ilze Bot, Bart J. M. van Vlijmen, Niek van Bree, Martine Bot, Kim L. L. Habets, Tom G. H. Keulers, Johan van der Vlag, Thomas G. Cotter, Theo J. C. van Berkel, Erik A. L. Biessen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/03205742549a4e9196533178b4a8d0fd
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spelling	oai:doaj.org-article:03205742549a4e9196533178b4a8d0fd2021-12-02T12:31:55ZLeukocyte Bim deficiency does not impact atherogenesis in ldlr −/− mice, despite a pronounced induction of autoimmune inflammation10.1038/s41598-017-02771-42045-2322https://doaj.org/article/03205742549a4e9196533178b4a8d0fd2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02771-4https://doaj.org/toc/2045-2322Abstract 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.Lieve TemmermanMarijke M. WestraIlze BotBart J. M. van VlijmenNiek van BreeMartine BotKim L. L. HabetsTom G. H. KeulersJohan van der VlagThomas G. CotterTheo J. C. van BerkelErik A. L. BiessenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lieve Temmerman Marijke M. Westra Ilze Bot Bart J. M. van Vlijmen Niek van Bree Martine Bot Kim L. L. Habets Tom G. H. Keulers Johan van der Vlag Thomas G. Cotter Theo J. C. van Berkel Erik A. L. Biessen Leukocyte Bim deficiency does not impact atherogenesis in ldlr −/− mice, despite a pronounced induction of autoimmune inflammation
description	Abstract 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.
format	article
author	Lieve Temmerman Marijke M. Westra Ilze Bot Bart J. M. van Vlijmen Niek van Bree Martine Bot Kim L. L. Habets Tom G. H. Keulers Johan van der Vlag Thomas G. Cotter Theo J. C. van Berkel Erik A. L. Biessen
author_facet	Lieve Temmerman Marijke M. Westra Ilze Bot Bart J. M. van Vlijmen Niek van Bree Martine Bot Kim L. L. Habets Tom G. H. Keulers Johan van der Vlag Thomas G. Cotter Theo J. C. van Berkel Erik A. L. Biessen
author_sort	Lieve Temmerman
title	Leukocyte Bim deficiency does not impact atherogenesis in ldlr −/− mice, despite a pronounced induction of autoimmune inflammation
title_short	Leukocyte Bim deficiency does not impact atherogenesis in ldlr −/− mice, despite a pronounced induction of autoimmune inflammation
title_full	Leukocyte Bim deficiency does not impact atherogenesis in ldlr −/− mice, despite a pronounced induction of autoimmune inflammation
title_fullStr	Leukocyte Bim deficiency does not impact atherogenesis in ldlr −/− mice, despite a pronounced induction of autoimmune inflammation
title_full_unstemmed	Leukocyte Bim deficiency does not impact atherogenesis in ldlr −/− mice, despite a pronounced induction of autoimmune inflammation
title_sort	leukocyte bim deficiency does not impact atherogenesis in ldlr −/− mice, despite a pronounced induction of autoimmune inflammation
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/03205742549a4e9196533178b4a8d0fd
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Leukocyte Bim deficiency does not impact atherogenesis in ldlr −/− mice, despite a pronounced induction of autoimmune inflammation

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