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标题：Angiotensin II synergizes with BAFF to promote atheroprotective regulatory B cells
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作者：Padmapriya Ponnuswamy ; Jeremie Joffre ; Olivier Herbin 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2017
卷号：7
期号：1
DOI：10.1038/s41598-017-04438-6
语种：English
出版社：Springer Nature
摘要：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.