| First Author | Ponnuswamy P | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Issue | 1 | Pages | 4111 |
| PubMed ID | 28646220 | Mgi Jnum | J:270569 |
| Mgi Id | MGI:6278884 | Doi | 10.1038/s41598-017-04438-6 |
| Citation | Ponnuswamy P, et al. (2017) Angiotensin II synergizes with BAFF to promote atheroprotective regulatory B cells. Sci Rep 7(1):4111 |
| abstractText | 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. |
