Deficiency of germinal center kinase TRAF2 and NCK-interacting kinase (TNIK) in B cells does not affect atherosclerosis
BackgroundAtherosclerosis 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 germina...
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| Format: | Article |
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2023.1171764/full |
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| author | Bram W. van Os Bram W. van Os Bram W. van Os Pascal J. H. Kusters Pascal J. H. Kusters Pascal J. H. Kusters Myrthe den Toom Myrthe den Toom Myrthe den Toom Linda Beckers Linda Beckers Linda Beckers Claudia M. van Tiel Claudia M. van Tiel Claudia M. van Tiel Winnie G. Vos Winnie G. Vos Winnie G. Vos Elize de Jong Arnd Kieser Cindy van Roomen Cindy van Roomen Cindy van Roomen Christoph J. Binder Myrthe E. Reiche Myrthe E. Reiche Myrthe E. Reiche Menno P. de Winther Menno P. de Winther Menno P. de Winther Laura A. Bosmans Laura A. Bosmans Laura A. Bosmans Esther Lutgens Esther Lutgens Esther Lutgens Esther Lutgens |
| author_facet | Bram W. van Os Bram W. van Os Bram W. van Os Pascal J. H. Kusters Pascal J. H. Kusters Pascal J. H. Kusters Myrthe den Toom Myrthe den Toom Myrthe den Toom Linda Beckers Linda Beckers Linda Beckers Claudia M. van Tiel Claudia M. van Tiel Claudia M. van Tiel Winnie G. Vos Winnie G. Vos Winnie G. Vos Elize de Jong Arnd Kieser Cindy van Roomen Cindy van Roomen Cindy van Roomen Christoph J. Binder Myrthe E. Reiche Myrthe E. Reiche Myrthe E. Reiche Menno P. de Winther Menno P. de Winther Menno P. de Winther Laura A. Bosmans Laura A. Bosmans Laura A. Bosmans Esther Lutgens Esther Lutgens Esther Lutgens Esther Lutgens |
| author_sort | Bram W. van Os |
| collection | DOAJ |
| description | BackgroundAtherosclerosis 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.ObjectiveWe here investigate the role of TNIK-deficient B cells in atherosclerosis.ResultsApoE−/−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.ConclusionWe here conclude that in hyperlipidemic ApoE−/− mice, B cell specific TNIK deficiency does not affect atherosclerosis. |
| first_indexed | 2024-04-09T14:18:46Z |
| format | Article |
| id | doaj.art-b457cc8d45844f5ca3e8e23782d56612 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-04-09T14:18:46Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-b457cc8d45844f5ca3e8e23782d566122023-05-05T05:46:29ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2023-05-011010.3389/fcvm.2023.11717641171764Deficiency of germinal center kinase TRAF2 and NCK-interacting kinase (TNIK) in B cells does not affect atherosclerosisBram W. van Os0Bram W. van Os1Bram W. van Os2Pascal J. H. Kusters3Pascal J. H. Kusters4Pascal J. H. Kusters5Myrthe den Toom6Myrthe den Toom7Myrthe den Toom8Linda Beckers9Linda Beckers10Linda Beckers11Claudia M. van Tiel12Claudia M. van Tiel13Claudia M. van Tiel14Winnie G. Vos15Winnie G. Vos16Winnie G. Vos17Elize de Jong18Arnd Kieser19Cindy van Roomen20Cindy van Roomen21Cindy van Roomen22Christoph J. Binder23Myrthe E. Reiche24Myrthe E. Reiche25Myrthe E. Reiche26Menno P. de Winther27Menno P. de Winther28Menno P. de Winther29Laura A. Bosmans30Laura A. Bosmans31Laura A. Bosmans32Esther Lutgens33Esther Lutgens34Esther Lutgens35Esther Lutgens36Department of Medical Biochemistry, Amsterdam UMC Location University of Amsterdam, Amsterdam, NetherlandsAmsterdam Cardiovascular Sciences, Atherosclerosis & Ischemic Syndromes, Amsterdam, NetherlandsAmsterdam Immunity and Infection, Amsterdam UMC, Amsterdam, NetherlandsDepartment of Medical Biochemistry, Amsterdam UMC Location University of Amsterdam, Amsterdam, NetherlandsAmsterdam Cardiovascular Sciences, Atherosclerosis & Ischemic Syndromes, Amsterdam, NetherlandsAmsterdam Immunity and Infection, Amsterdam UMC, Amsterdam, NetherlandsDepartment of Medical Biochemistry, Amsterdam UMC Location University of Amsterdam, Amsterdam, NetherlandsAmsterdam Cardiovascular Sciences, Atherosclerosis & Ischemic Syndromes, Amsterdam, NetherlandsAmsterdam Immunity and Infection, Amsterdam UMC, Amsterdam, NetherlandsDepartment of Medical Biochemistry, Amsterdam UMC Location University of Amsterdam, Amsterdam, NetherlandsAmsterdam Cardiovascular Sciences, Atherosclerosis & Ischemic Syndromes, Amsterdam, NetherlandsAmsterdam Immunity and Infection, Amsterdam UMC, Amsterdam, NetherlandsDepartment of Medical Biochemistry, Amsterdam UMC Location University of Amsterdam, Amsterdam, NetherlandsAmsterdam Cardiovascular Sciences, Atherosclerosis & Ischemic Syndromes, Amsterdam, NetherlandsAmsterdam Immunity and Infection, Amsterdam UMC, Amsterdam, NetherlandsDepartment of Medical Biochemistry, Amsterdam UMC Location University of Amsterdam, Amsterdam, NetherlandsAmsterdam Cardiovascular Sciences, Atherosclerosis & Ischemic Syndromes, Amsterdam, NetherlandsAmsterdam Immunity and Infection, Amsterdam UMC, Amsterdam, NetherlandsDepartment of Medical Biochemistry, Amsterdam UMC Location University of Amsterdam, Amsterdam, NetherlandsResearch Unit Signaling and Translation, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, GermanyDepartment of Medical Biochemistry, Amsterdam UMC Location University of Amsterdam, Amsterdam, NetherlandsAmsterdam Cardiovascular Sciences, Atherosclerosis & Ischemic Syndromes, Amsterdam, NetherlandsAmsterdam Immunity and Infection, Amsterdam UMC, Amsterdam, NetherlandsDepartment of Laboratory Medicine, Medical University of Vienna, Vienna, AustriaDepartment of Medical Biochemistry, Amsterdam UMC Location University of Amsterdam, Amsterdam, NetherlandsAmsterdam Cardiovascular Sciences, Atherosclerosis & Ischemic Syndromes, Amsterdam, NetherlandsAmsterdam Immunity and Infection, Amsterdam UMC, Amsterdam, NetherlandsDepartment of Medical Biochemistry, Amsterdam UMC Location University of Amsterdam, Amsterdam, NetherlandsAmsterdam Cardiovascular Sciences, Atherosclerosis & Ischemic Syndromes, Amsterdam, NetherlandsAmsterdam Immunity and Infection, Amsterdam UMC, Amsterdam, NetherlandsDepartment of Medical Biochemistry, Amsterdam UMC Location University of Amsterdam, Amsterdam, NetherlandsAmsterdam Cardiovascular Sciences, Atherosclerosis & Ischemic Syndromes, Amsterdam, NetherlandsAmsterdam Immunity and Infection, Amsterdam UMC, Amsterdam, NetherlandsDepartment of Medical Biochemistry, Amsterdam UMC Location University of Amsterdam, Amsterdam, NetherlandsInstitute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-Universität, Munich, GermanyGerman Center for Cardiovascular Research (DZHK), Partner site Munich Heart Alliance, Ludwig-Maximilians-Universität München, GermanyDepartment of Cardiovascular Medicine and Immunology, Mayo Clinic, Rochester, MN, United StatesBackgroundAtherosclerosis 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.ObjectiveWe here investigate the role of TNIK-deficient B cells in atherosclerosis.ResultsApoE−/−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.ConclusionWe here conclude that in hyperlipidemic ApoE−/− mice, B cell specific TNIK deficiency does not affect atherosclerosis.https://www.frontiersin.org/articles/10.3389/fcvm.2023.1171764/fullTNIKB cellssignalingatherosclerosisIgA |
| spellingShingle | Bram W. van Os Bram W. van Os Bram W. van Os Pascal J. H. Kusters Pascal J. H. Kusters Pascal J. H. Kusters Myrthe den Toom Myrthe den Toom Myrthe den Toom Linda Beckers Linda Beckers Linda Beckers Claudia M. van Tiel Claudia M. van Tiel Claudia M. van Tiel Winnie G. Vos Winnie G. Vos Winnie G. Vos Elize de Jong Arnd Kieser Cindy van Roomen Cindy van Roomen Cindy van Roomen Christoph J. Binder Myrthe E. Reiche Myrthe E. Reiche Myrthe E. Reiche Menno P. de Winther Menno P. de Winther Menno P. de Winther Laura A. Bosmans Laura A. Bosmans Laura A. Bosmans Esther Lutgens Esther Lutgens Esther Lutgens Esther Lutgens Deficiency of germinal center kinase TRAF2 and NCK-interacting kinase (TNIK) in B cells does not affect atherosclerosis Frontiers in Cardiovascular Medicine TNIK B cells signaling atherosclerosis IgA |
| title | Deficiency of germinal center kinase TRAF2 and NCK-interacting kinase (TNIK) in B cells does not affect atherosclerosis |
| title_full | Deficiency of germinal center kinase TRAF2 and NCK-interacting kinase (TNIK) in B cells does not affect atherosclerosis |
| title_fullStr | Deficiency of germinal center kinase TRAF2 and NCK-interacting kinase (TNIK) in B cells does not affect atherosclerosis |
| title_full_unstemmed | Deficiency of germinal center kinase TRAF2 and NCK-interacting kinase (TNIK) in B cells does not affect atherosclerosis |
| title_short | Deficiency of germinal center kinase TRAF2 and NCK-interacting kinase (TNIK) in B cells does not affect atherosclerosis |
| title_sort | deficiency of germinal center kinase traf2 and nck interacting kinase tnik in b cells does not affect atherosclerosis |
| topic | TNIK B cells signaling atherosclerosis IgA |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2023.1171764/full |
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