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van Os, B.W.* ; Kusters, P.J.H.* ; den Toom, M.* ; Beckers, L.* ; van Tiel, C.M.* ; Vos, W.G.* ; de Jong, E.* ; Kieser, A. ; van Roomen, C.* ; Binder, C.J.* ; Reiche, M.E.* ; de Winther, M.P.* ; Bosmans, L.A.* ; Lutgens, E.*

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

Front. Cardiovasc. Med. 10:1171764 (2023)
DOI PMC
Creative Commons Lizenzvertrag
Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.
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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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords B Cells ; Iga ; Tnik ; Atherosclerosis ; Signaling; Oxidation-specific Epitopes; Inflammatory-bowel; Lmp1; Cd40; Macrophages; Pathway; Targets
ISSN (print) / ISBN 2297-055X
e-ISSN 2297-055X
Quellenangaben Volume: 10, Issue: , Pages: , Article Number: 1171764 Supplement: ,
Publisher Frontiers
Publishing Place Lausanne
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Research Unit Signaling and Translation (SAT)
Grants European Research Council (ERC)