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

Autor:	van Os BW; Department of Medical Biochemistry, Amsterdam UMC Location University of Amsterdam, Amsterdam, Netherlands.; Amsterdam Cardiovascular Sciences, Atherosclerosis & Ischemic Syndromes, Amsterdam, Netherlands.; Amsterdam Immunity and Infection, Amsterdam UMC, Amsterdam, Netherlands., Kusters PJH; Department of Medical Biochemistry, Amsterdam UMC Location University of Amsterdam, Amsterdam, Netherlands.; Amsterdam Cardiovascular Sciences, Atherosclerosis & Ischemic Syndromes, Amsterdam, Netherlands.; Amsterdam Immunity and Infection, Amsterdam UMC, Amsterdam, Netherlands., den Toom M; Department of Medical Biochemistry, Amsterdam UMC Location University of Amsterdam, Amsterdam, Netherlands.; Amsterdam Cardiovascular Sciences, Atherosclerosis & Ischemic Syndromes, Amsterdam, Netherlands.; Amsterdam Immunity and Infection, Amsterdam UMC, Amsterdam, Netherlands., Beckers L; Department of Medical Biochemistry, Amsterdam UMC Location University of Amsterdam, Amsterdam, Netherlands.; Amsterdam Cardiovascular Sciences, Atherosclerosis & Ischemic Syndromes, Amsterdam, Netherlands.; Amsterdam Immunity and Infection, Amsterdam UMC, Amsterdam, Netherlands., van Tiel CM; Department of Medical Biochemistry, Amsterdam UMC Location University of Amsterdam, Amsterdam, Netherlands.; Amsterdam Cardiovascular Sciences, Atherosclerosis & Ischemic Syndromes, Amsterdam, Netherlands.; Amsterdam Immunity and Infection, Amsterdam UMC, Amsterdam, Netherlands., Vos WG; Department of Medical Biochemistry, Amsterdam UMC Location University of Amsterdam, Amsterdam, Netherlands.; Amsterdam Cardiovascular Sciences, Atherosclerosis & Ischemic Syndromes, Amsterdam, Netherlands.; Amsterdam Immunity and Infection, Amsterdam UMC, Amsterdam, Netherlands., de Jong E; Department of Medical Biochemistry, Amsterdam UMC Location University of Amsterdam, Amsterdam, Netherlands., Kieser A; Research Unit Signaling and Translation, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany., van Roomen C; Department of Medical Biochemistry, Amsterdam UMC Location University of Amsterdam, Amsterdam, Netherlands.; Amsterdam Cardiovascular Sciences, Atherosclerosis & Ischemic Syndromes, Amsterdam, Netherlands.; Amsterdam Immunity and Infection, Amsterdam UMC, Amsterdam, Netherlands., Binder CJ; Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria., Reiche ME; Department of Medical Biochemistry, Amsterdam UMC Location University of Amsterdam, Amsterdam, Netherlands.; Amsterdam Cardiovascular Sciences, Atherosclerosis & Ischemic Syndromes, Amsterdam, Netherlands.; Amsterdam Immunity and Infection, Amsterdam UMC, Amsterdam, Netherlands., de Winther MP; Department of Medical Biochemistry, Amsterdam UMC Location University of Amsterdam, Amsterdam, Netherlands.; Amsterdam Cardiovascular Sciences, Atherosclerosis & Ischemic Syndromes, Amsterdam, Netherlands.; Amsterdam Immunity and Infection, Amsterdam UMC, Amsterdam, Netherlands., Bosmans LA; Department of Medical Biochemistry, Amsterdam UMC Location University of Amsterdam, Amsterdam, Netherlands.; Amsterdam Cardiovascular Sciences, Atherosclerosis & Ischemic Syndromes, Amsterdam, Netherlands.; Amsterdam Immunity and Infection, Amsterdam UMC, Amsterdam, Netherlands., Lutgens E; Department of Medical Biochemistry, Amsterdam UMC Location University of Amsterdam, Amsterdam, Netherlands.; Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-Universität, Munich, Germany.; German Center for Cardiovascular Research (DZHK), Partner site Munich Heart Alliance, Ludwig-Maximilians-Universität München, Germany.; Department of Cardiovascular Medicine and Immunology, Mayo Clinic, Rochester, MN, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in cardiovascular medicine [Front Cardiovasc Med] 2023 May 05; Vol. 10, pp. 1171764. Date of Electronic Publication: 2023 May 05 (Print Publication: 2023).
DOI:	10.3389/fcvm.2023.1171764
Abstrakt:	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/fl CD19-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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (© 2023 van Os, Kusters, den Toom, Beckers, van Tiel, Vos, de Jong, Kieser, van Roomen, Binder, Reiche, de Winther, Bosmans and Lutgens.)
Databáze:	MEDLINE
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