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Journal Articles Scientific Reports Year : 2017

Angiotensin II synergizes with BAFF to promote atheroprotective regulatory B cells

Padmapriya Ponnuswamy
  • Function : Author
Olivier Herbin
  • Function : Author
Bruno Esposito
  • Function : Author
Ludivine Laurans
  • Function : Author
Christoph J Binder
  • Function : Author
Thomas F Tedder
  • Function : Author
Lynda Zeboudj
  • Function : Author
Xavier Loyer
  • Function : Author
Andreas Giraud
  • Function : Author
Yujiao Zhang
  • Function : Author
Alain Tedgui
  • Function : Author
Ziad Mallat
  • Function : Author
Hafid Ait-Oufella
  • Function : Author

Abstract

Angiotensin II (AngII) promotes hypertension, atherogenesis, vascular aneurysm and impairs postischemic 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 CD1d hi CD5 + 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.
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hal-04022889 , version 1 (10-03-2023)

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Padmapriya Ponnuswamy, Jeremie Joffre, Olivier Herbin, Bruno Esposito, Ludivine Laurans, et al.. Angiotensin II synergizes with BAFF to promote atheroprotective regulatory B cells. Scientific Reports, 2017, 7 (1), pp.4111. ⟨10.1038/s41598-017-04438-6⟩. ⟨hal-04022889⟩
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