Cargando…

Angiotensin II synergizes with BAFF to promote atheroprotective regulatory B cells

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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, Mallat, Ziad, Ait-Oufella, Hafid
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482806/
https://www.ncbi.nlm.nih.gov/pubmed/28646220
http://dx.doi.org/10.1038/s41598-017-04438-6
_version_ 1783245630246748160
author 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
Mallat, Ziad
Ait-Oufella, Hafid
author_facet 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
Mallat, Ziad
Ait-Oufella, Hafid
author_sort Ponnuswamy, Padmapriya
collection PubMed
description 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 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.
format Online
Article
Text
id pubmed-5482806
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-54828062017-06-26 Angiotensin II synergizes with BAFF to promote atheroprotective regulatory B cells 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 Mallat, Ziad Ait-Oufella, Hafid Sci Rep 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 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. Nature Publishing Group UK 2017-06-23 /pmc/articles/PMC5482806/ /pubmed/28646220 http://dx.doi.org/10.1038/s41598-017-04438-6 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
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
Mallat, Ziad
Ait-Oufella, Hafid
Angiotensin II synergizes with BAFF to promote atheroprotective regulatory B cells
title Angiotensin II synergizes with BAFF to promote atheroprotective regulatory B cells
title_full Angiotensin II synergizes with BAFF to promote atheroprotective regulatory B cells
title_fullStr Angiotensin II synergizes with BAFF to promote atheroprotective regulatory B cells
title_full_unstemmed Angiotensin II synergizes with BAFF to promote atheroprotective regulatory B cells
title_short Angiotensin II synergizes with BAFF to promote atheroprotective regulatory B cells
title_sort angiotensin ii synergizes with baff to promote atheroprotective regulatory b cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482806/
https://www.ncbi.nlm.nih.gov/pubmed/28646220
http://dx.doi.org/10.1038/s41598-017-04438-6
work_keys_str_mv AT ponnuswamypadmapriya angiotensiniisynergizeswithbafftopromoteatheroprotectiveregulatorybcells
AT joffrejeremie angiotensiniisynergizeswithbafftopromoteatheroprotectiveregulatorybcells
AT herbinolivier angiotensiniisynergizeswithbafftopromoteatheroprotectiveregulatorybcells
AT espositobruno angiotensiniisynergizeswithbafftopromoteatheroprotectiveregulatorybcells
AT lauransludivine angiotensiniisynergizeswithbafftopromoteatheroprotectiveregulatorybcells
AT binderchristophj angiotensiniisynergizeswithbafftopromoteatheroprotectiveregulatorybcells
AT tedderthomasf angiotensiniisynergizeswithbafftopromoteatheroprotectiveregulatorybcells
AT zeboudjlynda angiotensiniisynergizeswithbafftopromoteatheroprotectiveregulatorybcells
AT loyerxavier angiotensiniisynergizeswithbafftopromoteatheroprotectiveregulatorybcells
AT giraudandreas angiotensiniisynergizeswithbafftopromoteatheroprotectiveregulatorybcells
AT zhangyujiao angiotensiniisynergizeswithbafftopromoteatheroprotectiveregulatorybcells
AT tedguialain angiotensiniisynergizeswithbafftopromoteatheroprotectiveregulatorybcells
AT mallatziad angiotensiniisynergizeswithbafftopromoteatheroprotectiveregulatorybcells
AT aitoufellahafid angiotensiniisynergizeswithbafftopromoteatheroprotectiveregulatorybcells