Frontiers in Cardiovascular Medicine (May 2023)

Deficiency of germinal center kinase TRAF2 and NCK-interacting kinase (TNIK) in B cells does not affect atherosclerosis

  • Bram W. van Os,
  • Bram W. van Os,
  • Bram W. van Os,
  • Pascal J. H. Kusters,
  • Pascal J. H. Kusters,
  • Pascal J. H. Kusters,
  • Myrthe den Toom,
  • Myrthe den Toom,
  • Myrthe den Toom,
  • Linda Beckers,
  • Linda Beckers,
  • Linda Beckers,
  • Claudia M. van Tiel,
  • Claudia M. van Tiel,
  • Claudia M. van Tiel,
  • Winnie G. Vos,
  • Winnie G. Vos,
  • Winnie G. Vos,
  • Elize de Jong,
  • Arnd Kieser,
  • Cindy van Roomen,
  • Cindy van Roomen,
  • Cindy van Roomen,
  • Christoph J. Binder,
  • Myrthe E. Reiche,
  • Myrthe E. Reiche,
  • Myrthe E. Reiche,
  • Menno P. de Winther,
  • Menno P. de Winther,
  • Menno P. de Winther,
  • Laura A. Bosmans,
  • Laura A. Bosmans,
  • Laura A. Bosmans,
  • Esther Lutgens,
  • Esther Lutgens,
  • Esther Lutgens,
  • Esther Lutgens

DOI
https://doi.org/10.3389/fcvm.2023.1171764
Journal volume & issue
Vol. 10

Abstract

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BackgroundAtherosclerosis is the underlying cause of many cardiovascular diseases, such as myocardial infarction or stroke. B cells, and their production of pro- and anti-atherogenic antibodies, play an important role in atherosclerosis. In B cells, TRAF2 and NCK-interacting Kinase (TNIK), a germinal center kinase, was shown to bind to TNF-receptor associated factor 6 (TRAF6), and to be involved in JNK and NF-κB signaling in human B cells, a pathway associated with antibody production.ObjectiveWe here investigate the role of TNIK-deficient B cells in atherosclerosis.ResultsApoE−/−TNIKfl/fl (TNIKBWT) and ApoE−/−TNIKfl/flCD19-cre (TNIKBKO) mice received a high cholesterol diet for 10 weeks. Atherosclerotic plaque area did not differ between TNIKBKO and TNIKBWT mice, nor was there any difference in plaque necrotic core, macrophage, T cell, α-SMA and collagen content. B1 and B2 cell numbers did not change in TNIKBKO mice, and marginal zone, follicular or germinal center B cells were unaffected. Total IgM and IgG levels, as well as oxidation specific epitope (OSE) IgM and IgG levels, did not change in absence of B cell TNIK. In contrast, plasma IgA levels were decreased in TNIKBKO mice, whereas the number of IgA+ B cells in intestinal Peyer's patches increased. No effects could be detected on T cell or myeloid cell numbers or subsets.ConclusionWe here conclude that in hyperlipidemic ApoE−/− mice, B cell specific TNIK deficiency does not affect atherosclerosis.

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