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

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dc.contributor.authorTemmerman, Lieve
dc.contributor.authorWestra, Marijke M.
dc.contributor.authorBot, Ilze
dc.contributor.authorvan Vlijmen, Bart J. M.
dc.contributor.authorVan Bree, Niek
dc.contributor.authorBot, Martine
dc.contributor.authorHabets, Kim L. L.
dc.contributor.authorKeulers, Tom G. H.
dc.contributor.authorvan der Vlag, Johan
dc.contributor.authorCotter, Thomas G.
dc.contributor.authorvan Berkel, Theo J. C.
dc.contributor.authorBiessen, Erik A. L.
dc.date.accessioned2017-06-26T14:56:13Z
dc.date.available2017-06-26T14:56:13Z
dc.date.issued2017-06-08
dc.date.updated2017-06-26T14:52:01Z
dc.description.abstractProapoptotic 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.en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleid3086
dc.identifier.citationTemmerman, L., Westra, M. M., Bot, I., Vlijmen, B. J. M. v., Bree, N. V., Bot, M., Habets, K. L. L., Keulers, T. G. H., Vlag, J. v. d., Cotter, T. G., Berkel, T. J. C. v. and Biessen, E. A. L. (2017) 'Leukocyte Bim deficiency does not impact atherogenesis in ldlr −/− mice, despite a pronounced induction of autoimmune inflammation', Scientific Reports, 7(1), 3086. doi:10.1038/s41598-017-02771-4en
dc.identifier.doi10.1038/s41598-017-02771-4
dc.identifier.endpage3086-11en
dc.identifier.issn2045-2322
dc.identifier.issued1en
dc.identifier.journaltitleScientific Reportsen
dc.identifier.startpage3086-1en
dc.identifier.urihttps://hdl.handle.net/10468/4190
dc.identifier.volume7en
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.rights© The Authors 2017. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visiten
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAtherosclerosisen
dc.subjectAutoimmunityen
dc.subjectChronic inflammationen
dc.subjectExperimental models of diseaseen
dc.titleLeukocyte Bim deficiency does not impact atherogenesis in ldlr -/- mice, despite a pronounced induction of autoimmune inflammationen
dc.typeArticle (peer-reviewed)en
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