Angiotensin II synergizes with BAFF to promote atheroprotective regulatory B cells.

Published online

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Ponnuswamy, P; Joffre, J; Herbin, O; Esposito, B; Laurans, L; Binder, CJ; Tedder, TF; Zeboudj, L; Loyer, X; Giraud, A; Zhang, Y; Tedgui, A; Mallat, Z; Ait-Oufella, H

Published Date

  • June 23, 2017

Published In

Volume / Issue

  • 7 / 1

Start / End Page

  • 4111 -

PubMed ID

  • 28646220

Pubmed Central ID

  • 28646220

Electronic International Standard Serial Number (EISSN)

  • 2045-2322

Digital Object Identifier (DOI)

  • 10.1038/s41598-017-04438-6

Language

  • eng

Conference Location

  • England