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

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

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=10

YEAR=2023

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2023.1171764

DOI=10.3389/fcvm.2023.1171764

ISSN=2297-055X

ABSTRACT=<sec><title>Background</title><p>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.</p></sec><sec><title>Objective</title><p>We here investigate the role of TNIK-deficient B cells in atherosclerosis.</p></sec><sec><title>Results</title><p><italic>ApoE<sup>−/−</sup>TNIK<sup>fl/fl</sup></italic> (<italic>TNIK<sup>BWT</sup></italic>) and <italic>ApoE<sup>−/−</sup>TNIK<sup>fl/fl</sup>CD19-cre</italic> (<italic>TNIK<sup>BKO</sup></italic>) mice received a high cholesterol diet for 10 weeks. Atherosclerotic plaque area did not differ between <italic>TNIK<sup>BKO</sup></italic> and <italic>TNIK<sup>BWT</sup></italic> 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 <italic>TNIK<sup>BKO</sup></italic> 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 <italic>TNIK<sup>BKO</sup></italic> mice, whereas the number of IgA<sup>+</sup> B cells in intestinal Peyer's patches increased. No effects could be detected on T cell or myeloid cell numbers or subsets.</p></sec><sec><title>Conclusion</title><p>We here conclude that in hyperlipidemic <italic>ApoE<sup>−/−</sup></italic> mice, B cell specific TNIK deficiency does not affect atherosclerosis.</p></sec>