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

Bram W van Os; Pascal J H Kusters; Myrthe den Toom; Linda Beckers; Claudia M van Tiel; Winnie G Vos; Elize de Jong; Arnd Kieser; Cindy van Roomen; Christoph J Binder; Myrthe E Reiche; Menno P de Winther; Laura A Bosmans; Esther Lutgens

doi:10.3389/fcvm.2023.1171764

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

Bram W van Os, Pascal J H Kusters, Myrthe den Toom, Linda Beckers, Claudia M van Tiel, Winnie G Vos, Elize de Jong, Arnd Kieser, Cindy van Roomen, Christoph J Binder, Myrthe E Reiche, Menno P de Winther, Laura A Bosmans^*, Esther Lutgens

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Article number	1171764
Number of pages	12
Journal	Frontiers in Cardiovascular Medicine
Volume	10
DOIs	https://doi.org/10.3389/fcvm.2023.1171764
Publication status	Published - 5 May 2023
Externally published	Yes

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10.3389/fcvm.2023.1171764Licence: CC BY

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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. (2023). Deficiency of germinal center kinase TRAF2 and NCK-interacting kinase (TNIK) in B cells does not affect atherosclerosis. Frontiers in Cardiovascular Medicine, 10, Article 1171764. https://doi.org/10.3389/fcvm.2023.1171764

@article{a4c869cd20044f81ba7c8ff4da2ac3b4,

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

abstract = "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.",

author = "{van Os}, {Bram W} and Kusters, {Pascal J H} and {den Toom}, Myrthe and Linda Beckers and {van Tiel}, {Claudia M} and Vos, {Winnie G} and {de Jong}, Elize and Arnd Kieser and {van Roomen}, Cindy and Binder, {Christoph J} and Reiche, {Myrthe E} and {de Winther}, {Menno P} and Bosmans, {Laura A} and Esther Lutgens",

note = "Publisher Copyright: 2023 van Os, Kusters, den Toom, Beckers, van Tiel, Vos, de Jong, Kieser, van Roomen, Binder, Reiche, de Winther, Bosmans and Lutgens.",

year = "2023",

month = may,

day = "5",

doi = "10.3389/fcvm.2023.1171764",

language = "English",

volume = "10",

journal = "Frontiers in Cardiovascular Medicine",

issn = "2297-055X",

publisher = "Frontiers Media S. A.",

}

van Os, BW, Kusters, PJH, den Toom, M, Beckers, L, van Tiel, CM, Vos, WG, de Jong, E, Kieser, A, van Roomen, C, Binder, CJ, Reiche, ME, de Winther, MP, Bosmans, LA & Lutgens, E 2023, 'Deficiency of germinal center kinase TRAF2 and NCK-interacting kinase (TNIK) in B cells does not affect atherosclerosis', Frontiers in Cardiovascular Medicine, vol. 10, 1171764. https://doi.org/10.3389/fcvm.2023.1171764

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 - 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 - 2023/5/5

Y1 - 2023/5/5

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.

U2 - 10.3389/fcvm.2023.1171764

DO - 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 -

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

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