Angiotensin II synergizes with BAFF to promote atheroprotective regulatory B cells.
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Authors
Ponnuswamy, Padmapriya
Joffre, Jeremie
Herbin, Olivier
Esposito, Bruno
Laurans, Ludivine
Binder, Christoph J
Tedder, Thomas F
Zeboudj, Lynda
Loyer, Xavier
Giraud, Andreas
Zhang, Yujiao
Tedgui, Alain
Ait-Oufella, Hafid
Publication Date
2017-06-23Journal Title
Sci Rep
ISSN
2045-2322
Publisher
Springer Science and Business Media LLC
Volume
7
Issue
1
Pages
4111
Language
eng
Type
Article
This Version
VoR
Physical Medium
Electronic
Metadata
Show full item recordCitation
Ponnuswamy, P., Joffre, J., Herbin, O., Esposito, B., Laurans, L., Binder, C. J., Tedder, T. F., et al. (2017). Angiotensin II synergizes with BAFF to promote atheroprotective regulatory B cells.. Sci Rep, 7 (1), 4111. https://doi.org/10.1038/s41598-017-04438-6
Abstract
Angiotensin II (AngII) promotes hypertension, atherogenesis, vascular aneurysm and impairs post-ischemic cardiac remodeling through concerted roles on vascular cells, monocytes and T lymphocytes. However, the role of AngII in B lymphocyte responses is largely unexplored. Here, we show that chronic B cell depletion (Baffr deficiency) significantly reduces atherosclerosis in Apoe -/- mice infused with AngII. While adoptive transfer of B cells in Apoe -/- /Baffr -/- mice reversed atheroprotection in the absence of AngII, infusion of AngII in B cell replenished Apoe -/- /Baffr -/- mice unexpectedly prevented the progression of atherosclerosis. Atheroprotection observed in these mice was associated with a significant increase in regulatory CD1dhiCD5+ B cells, which produced high levels of interleukin (IL)-10 (B10 cells). Replenishment of Apoe -/- /Baffr -/- mice with Il10 -/- B cells reversed AngII-induced B cell-dependent atheroprotection, thus highlighting a protective role of IL-10+ regulatory B cells in this setting. Transfer of AngII type 1A receptor deficient (Agtr1a -/-) B cells into Apoe -/- /Baffr -/- mice substantially reduced the production of IL-10 by B cells and prevented the AngII-dependent atheroprotective B cell phenotype. Consistent with the in vivo data, AngII synergized with BAFF to induce IL-10 production by B cells in vitro via AngII type 1A receptor. Our data demonstrate a previously unknown synergy between AngII and BAFF in inducing IL-10 production by B cells, resulting in atheroprotection.
Keywords
Cells, Cultured, Animals, Mice, Knockout, Mice, Disease Models, Animal, Angiotensin II, Receptor, Angiotensin, Type 1, Interleukin-10, Immunohistochemistry, Phenotype, Atherosclerosis, B-Cell Activating Factor, B-Lymphocytes, Regulatory, Biomarkers
Sponsorship
British Heart Foundation (PG/15/76/31756)
Identifiers
External DOI: https://doi.org/10.1038/s41598-017-04438-6
This record's URL: https://www.repository.cam.ac.uk/handle/1810/277314
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