| Autor: |
Padmapriya Ponnuswamy, Jeremie Joffre, Olivier Herbin, Bruno Esposito, Ludivine Laurans, Christoph J. Binder, Thomas F. Tedder, Lynda Zeboudj, Xavier Loyer, Andreas Giraud, Yujiao Zhang, Alain Tedgui, Ziad Mallat, Hafid Ait-Oufella |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| Předmět: |
|
| Zdroj: |
Scientific Reports, Vol 7, Iss 1, Pp 1-10 (2017) |
| Druh dokumentu: |
article |
| ISSN: |
2045-2322 |
| DOI: |
10.1038/s41598-017-04438-6 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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