PuSH - Publikationsserver des Helmholtz Zentrums München: Deficiency of germinal center kinase TRAF2 and NCK-interacting kinase (TNIK) in B cells does not affect atherosclerosis.

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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)

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Open Access Gold möglich sobald Verlagsversion bei der ZB eingereicht worden ist.

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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.

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Publikationstyp Artikel: Journalartikel

Dokumenttyp Wissenschaftlicher Artikel

Korrespondenzautor

Schlagwörter 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

Zeitschrift Frontiers in Cardiovascular Medicine

Quellenangaben Band: 10, Artikelnummer: 1171764

Verlag Frontiers

Verlagsort Lausanne

Nichtpatentliteratur Publikationen

Begutachtungsstatus Peer reviewed

Institut(e) Research Unit Signaling and Translation (SAT)

Förderungen European Research Council (ERC)