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

ABSTRACT:

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^-/-TNIK^fl/fl (TNIK^BWT) and ApoE^-/-TNIK^fl/flCD19-cre (TNIK^BKO) mice received a high cholesterol diet for 10 weeks. Atherosclerotic plaque area did not differ between TNIK^BKO and TNIK^BWT 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 TNIK^BKO 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 TNIK^BKO 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.

SUBMITTER: van Os BW 

PROVIDER: S-EPMC10196212 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature