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Image5_Deficiency of germinal center kinase TRAF2 and NCK-interacting kinase (TNIK) in B cells does not affect atherosclerosis.tif (724.92 kB)

Image5_Deficiency of germinal center kinase TRAF2 and NCK-interacting kinase (TNIK) in B cells does not affect atherosclerosis.tif

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posted on 2023-05-05, 04:30 authored by Bram W. van Os, Pascal J. H. Kusters, Myrthe den Toom, Linda Beckers, Claudia M. van Tiel, Winnie G. Vos, Elize de Jong, Arnd Kieser, Cindy van Roomen, Christoph J. Binder, Myrthe E. Reiche, Menno P. de Winther, Laura A. Bosmans, Esther Lutgens
Background

Atherosclerosis 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.

Objective

We here investigate the role of TNIK-deficient B cells in atherosclerosis.

Results

ApoE−/−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.

Conclusion

We here conclude that in hyperlipidemic ApoE−/− mice, B cell specific TNIK deficiency does not affect atherosclerosis.

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    Frontiers in Cardiovascular Medicine

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