TRAF3 regulates the effector function of regulatory T cells and humoral immune responses.
TRAF3 regulates the effector function of regulatory T cells and humoral immune responses.
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DOI：
10.1084/jem.20131019
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发表时间：
2014-01-13
期刊：
影响因子：
--
通讯作者：
Sun SC
中科院分区：
文献类型：
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作者：
Chang JH;Hu H;Jin J;Puebla-Osorio N;Xiao Y;Gilbert BE;Brink R;Ullrich SE;Sun SC
滤泡调节性T细胞的诱导和生发中心反应的控制需要衔接蛋白Traf 3，部分原因是Traf 3诱导ICOS的表达。调节性T细胞（Treg细胞）控制免疫应答的不同方面，但Treg细胞的效应子功能如何调节尚不完全清楚。在这里，我们确定了肿瘤坏死因子受体相关因子3（TRAF 3）作为调节Treg细胞功能。Treg细胞特异性消融TRAF 3损害了CD 4 T细胞的稳态，其特征在于Th 1型效应/记忆T细胞的增加。此外，Treg细胞中TRAF 3的消融导致滤泡T辅助细胞（TFH细胞）的抗原刺激活化增加，伴随着生发中心的形成和高亲和力IgG抗体的产生增加。尽管TRAF 3的缺失没有降低Treg细胞的总体频率，但它减弱了抗原刺激的滤泡Treg细胞（TFR细胞）的产生。Treg细胞中的TRAF 3信号传导是维持诱导型共刺激分子（ICOS）的高水平表达所必需的，而诱导型共刺激分子又是TFR细胞生成和抗体应答抑制所必需的。这些发现确立了TRAF 3在调节抗体应答中作为Treg细胞功能的介体，并表明TRAF 3在介导Treg细胞中ICOS表达中的作用。
The induction of follicular regulatory T cells and control of germinal center reactions require the adaptor protein Traf3, in part because of Traf3-induced expression of ICOS. Regulatory T cells (Treg cells) control different aspects of immune responses, but how the effector functions of Treg cells are regulated is incompletely understood. Here we identified TNF receptor–associated factor 3 (TRAF3) as a regulator of Treg cell function. Treg cell–specific ablation of TRAF3 impaired CD4 T cell homeostasis, characterized by an increase in the Th1 type of effector/memory T cells. Moreover, the ablation of TRAF3 in Treg cells resulted in increased antigen-stimulated activation of follicular T helper cells (TFH cells), coupled with heightened formation of germinal centers and production of high-affinity IgG antibodies. Although the loss of TRAF3 did not reduce the overall frequency of Treg cells, it attenuated the antigen-stimulated production of follicular Treg cells (TFR cells). TRAF3 signaling in Treg cells was required to maintain high level expression of inducible co-stimulator (ICOS), which in turn was required for TFR cell generation and inhibition of antibody responses. These findings establish TRAF3 as a mediator of Treg cell function in the regulation of antibody responses and suggest a role for TRAF3 in mediating ICOS expression in Treg cells.