Regulatory B cells improve ventricular remodeling after myocardial infarction by modulating monocyte migration.
Regulatory B cells improve ventricular remodeling after myocardial infarction by modulating monocyte migration.
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调节性 B 细胞通过调节单核细胞迁移改善心肌梗死后心室重塑
DOI：
10.1007/s00395-021-00886-4
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发表时间：
2021-07-24
影响因子：
9.5
通讯作者：
Cheng X
中科院分区：
文献类型：
--
作者：
Jiao J;He S;Wang Y;Lu Y;Gu M;Li D;Tang T;Nie S;Zhang M;Lv B;Li J;Xia N;Cheng X
过度激活的炎症反应导致心肌梗死(MI)后不良的室壁重构。调节性B细胞(Bregs)是新发现的B细胞亚群，在许多免疫和炎症相关疾病中具有免疫调节作用。我们的研究旨在确定Bregs扩张是否对心室重构产生有益的影响，并探讨其机制。在这里，我们发现Bregs过继转移改善了小鼠心肌梗死模型的心室重构，表现为改善了心功能，减少了瘢痕大小，减轻了间质纤维化，而不改变存活率。BREG基因转染组小鼠心脏中LY6嵌合细胞的浸润减少，而LY6克隆细胞的浸润未受影响。此外，补充Bregs对心肌中T细胞或中性粒细胞的蓄积没有影响。机制上，Bregs减少单核细胞C-C基序趋化因子受体2(CCR2)的表达，从而抑制外周血中促炎症单核细胞向心脏的募集和骨髓中的动员。用白介素10(IL-10)抗体处理后，BREG介导的心肌梗死保护作用被取消。最后，IL-10中和逆转了Bregs对单核细胞迁移和CCR2表达的影响。本研究提示Bregs通过减少CCR2介导的单核细胞募集和动员来限制心肌梗死后的心室重构。
Overactivated inflammatory responses contribute to adverse ventricular remodeling after myocardial infarction (MI). Regulatory B cells (Bregs) are a newly discovered subset of B cells with immunomodulatory roles in many immune and inflammation-related diseases. Our study aims to determine whether the expansion of Bregs exerts a beneficial effect on ventricular remodeling and explore the mechanisms involved. Here, we showed that adoptive transfer of Bregs ameliorated ventricular remodeling in a murine MI model, as demonstrated by improved cardiac function, decreased scar size and attenuated interstitial fibrosis without changing the survival rate. Reduced Ly6Chimonocyte infiltration was found in the hearts of the Breg-transferred mice, while the infiltration of Ly6Clomonocytes was not affected. In addition, the replenishment of Bregs had no effect on the myocardial accumulation of T cells or neutrophils. Mechanistically, Bregs reduced the expression of C–C motif chemokine receptor 2 (CCR2) in monocytes, which inhibited proinflammatory monocyte recruitment to the heart from the peripheral blood and mobilization from the bone marrow. Breg-mediated protection against MI was abrogated by treatment with an interleukin 10 (IL-10) antibody. Finally, IL-10 neutralization reversed the effect of Bregs on monocyte migration and CCR2 expression. The present study suggests a therapeutic value of Bregs in limiting ventricular remodeling after MI through decreasing CCR2-mediated monocyte recruitment and mobilization.
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影响因子：
7.4
作者：
Kalli F;Machiorlatti R;Battaglia F;Parodi A;Conteduca G;Ferrera F;Proietti M;Tardito S;Sanguineti M;Millo E;Fenoglio D;De Palma R;Inghirami G;Filaci G
通讯作者：
Filaci G
影响因子：
10.1
作者：
Foubert P;Kaneda MM;Varner JA
通讯作者：
Varner JA
影响因子：
12.4
作者：
Braza, F.;Chesne, J.;Brouard, S.
通讯作者：
Brouard, S.
影响因子：
11.3
作者：
Goodchild, Traci T.;Robinson, Keith A.;Chronos, Nicolas A. F.
通讯作者：
Chronos, Nicolas A. F.
影响因子：
37.8
作者：
Hayashidani, S;Tsutsui, H;Takeshita, A
通讯作者：
Takeshita, A