Inducible costimulator facilitates T-dependent B cell activation by augmenting IL-4 translation
Inducible costimulator facilitates T-dependent B cell activation by augmenting IL-4 translation
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DOI：
10.1016/j.molimm.2014.01.008
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发表时间：
2014-05-01
影响因子：
3.6
通讯作者：
Suh, Woong-Kyung
中科院分区：
文献类型：
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作者：
Gigoux, Mathieu;Lovato, Amanda;Suh, Woong-Kyung
诱导型共刺激分子（ICOS）在滤泡辅助T（Tfh）细胞中高度表达，Tfh细胞是迁移到B细胞区并促进生发中心反应的CD 4 T细胞亚群。尽管已知ICOS在免疫应答期间形成Tfh细胞群体中起关键作用，但其对Tfh细胞的效应子功能的贡献仍不清楚。使用活化的小鼠脾CD 4 T细胞，我们证明ICOS通过增强PI 3 K-AKT-mTOR信号级联来辅助TCR介导的信号转导，PI 3 K-AKT-mTOR信号级联导致p70 S6 K和4 E-BPI的过度磷酸化，已知这些事件增加帽依赖性mRNA翻译。因此，ICOS共刺激以PI 3 K依赖的方式促进IL-4 mRNA上多核糖体的形成。此外，我们表明，IL-4的供应成为T-依赖性B细胞活化的限制因素，在体外共培养过程中，当ICOS-PI 3 K信号轴在T细胞中被破坏。这种ICOS共刺激依赖的翻译控制可以确保在生发中心的T-B协作期间IL-4靶向递送至同源B细胞。(C)2014爱思唯尔有限公司版权所有。
The inducible costimulator (ICOS) is highly expressed in follicular helper T (Tfh) cells, a subset of CD4 T cells that migrate into the B cell zone and facilitate germinal center reactions. Although ICOS is known to play a critical role in forming the Tfh cell population during immune responses, its contribution to the effector functions of Tfh cells remains unclear. Using activated mouse splenic CD4 T cells we demonstrate that ICOS assists TCR-mediated signal transduction by potentiating the PI3K-AKT-mTOR signaling cascade that leads to hyper-phosphorylation of p70S6K and 4E-BPI, events that are known to augment cap-dependent mRNA translation. Consequently, ICOS costimulation promotes the formation of polysomes on IL-4 mRNA in a PI3K-dependent manner. Furthermore, we show that the supply of IL-4 becomes a limiting factor for T-dependent B cell activation during in vitro co-culture when the ICOS-PI3K signaling axis is disrupted in T cells. This ICOS costimulation-dependent translational control may ensure targeted delivery of IL-4 to cognate B cells during T-B collaborations in the germinal center. (C) 2014 Elsevier Ltd. All rights reserved.