Interleukin-10 from CD4(+) follicular regulatory T cells promotes the germinal center response.

Interleukin-10 from CD4(+) follicular regulatory T cells promotes the germinal center response.
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DOI:
10.1126/sciimmunol.aan4767
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发表时间:
2017-10-20
期刊:
影响因子:
24.8
通讯作者:
Craft J
Craft J
中科院分区:
医学1区
文献类型:
--
作者:
Laidlaw BJ;Lu Y;Amezquita RA;Weinstein JS;Vander Heiden JA;Gupta NT;Kleinstein SH;Kaech SM;Craft J

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CD 4+滤泡调节性T细胞(Tfr细胞)通过调节滤泡辅助性T细胞(Tfh细胞)和生发中心(GC)的发育来抑制B细胞应答。我们发现,Tfr细胞也可以促进GC反应,通过提供IL-10与淋巴细胞性脉络丛脑膜炎病毒(LCMV)急性感染后。B细胞对IL-10的感应对于GC反应的最佳发展是必要的。在缺乏Treg细胞衍生的IL-10的情况下形成的GC B细胞显示改变的暗区状态和转录因子FOXO 1的表达降低。IL-10促进活化B细胞中FOXO 1的核转位。这些数据表明,Tfr细胞在GC反应的微调中发挥多方面的作用,并将IL-10鉴定为Tfr细胞支持GC反应的重要介质。
CD4+ follicular regulatory T cells (Tfr cells) suppress B cell responses through modulation of follicular helper T cells (Tfh cells) and germinal center (GC) development. We found that Tfr cells also can promote the GC response through provision of IL-10 following acute infection with lymphocytic choriomeningitis virus (LCMV). Sensing of IL-10 by B cells was necessary for optimal development of the GC response. GC B cells formed in the absence of Treg-cell derived IL-10 displayed an altered dark zone state and decreased expression of the transcription factor FOXO1. IL-10 promoted nuclear translocation of FOXO1 in activated B cells. These data indicate that Tfr cells play a multifaceted role in the fine-tuning of the GC response and identify IL-10 as an important mediator by which Tfr cells support the GC reaction.
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