TY - JOUR
T1 - Deficiency of germinal center kinase TRAF2 and NCK-interacting kinase (TNIK) in B cells does not affect atherosclerosis
AU - van Os, Bram W.
AU - Kusters, Pascal J. H.
AU - den Toom, Myrthe
AU - Beckers, Linda
AU - van Tiel, Claudia M.
AU - Vos, Winnie G.
AU - de Jong, Elize
AU - Kieser, Arnd
AU - van Roomen, Cindy
AU - Binder, Christoph J.
AU - Reiche, Myrthe E.
AU - de Winther, Menno P.
AU - Bosmans, Laura A.
AU - Lutgens, Esther
N1 - Funding Information: This study was supported by the European Research Council (ERC consolidator grant to EL). Publisher Copyright: 2023 van Os, Kusters, den Toom, Beckers, van Tiel, Vos, de Jong, Kieser, van Roomen, Binder, Reiche, de Winther, Bosmans and Lutgens.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - B cells
KW - IgA
KW - TNIK
KW - atherosclerosis
KW - signaling
UR - http://www.scopus.com/inward/record.url?scp=85159871325&partnerID=8YFLogxK
U2 - https://doi.org/10.3389/fcvm.2023.1171764
DO - https://doi.org/10.3389/fcvm.2023.1171764
M3 - Article
C2 - 37215541
SN - 2297-055X
VL - 10
JO - Frontiers in cardiovascular medicine
JF - Frontiers in cardiovascular medicine
M1 - 1171764
ER -