Dectin-1-activated dendritic cells trigger potent antitumour immunity through the induction of Th9 cells.
Dectin-1-activated dendritic cells trigger potent antitumour immunity through the induction of Th9 cells.
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Dectin-1 激活的树突状细胞通过诱导 Th9 细胞触发有效的抗肿瘤免疫
DOI：
10.1038/ncomms12368
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发表时间：
2016-08-05
影响因子：
16.6
通讯作者：
Wang S
中科院分区：
文献类型：
--
作者：
Zhao Y;Chu X;Chen J;Wang Y;Gao S;Jiang Y;Zhu X;Tan G;Zhao W;Yi H;Xu H;Ma X;Lu Y;Yi Q;Wang S
树突状细胞（dc）中的Dectin-1信号传导在触发保护性抗真菌Th17反应中起重要作用。然而，dectin-1是否将dc导向初始抗肿瘤Th9细胞仍不清楚。在这里，我们发现由dectin-1激动剂激活的dc可以有效地促进初始CD4+ T细胞分化为Th9细胞。在dc中去除dectin-1完全消除了它们对dectin-1激动剂反应的th9极化能力。值得注意的是，dectin-1刺激dc会上调TNFSF15和OX40L，这对于dectin-1激活dc诱导的Th9细胞启动至关重要。在机制上，dectin-1激活Syk、Raf1和NF-κB信号通路，导致p50和RelB核易位以及TNFSF15和OX40L表达增加。此外，用dectin-1激活的dc免疫荷瘤小鼠可诱导有效的抗肿瘤反应，这种反应依赖于Th9细胞和IL-9，这是dectin-1激活的dc在体内诱导的。我们的研究结果表明，检测素-1激活的dc是Th9细胞和抗肿瘤免疫的强大诱导剂，可能具有重要的临床意义。树突状细胞根据所感知的微生物配体类型指示不同类型的T细胞反应。在小鼠模型中，通过Dectin-1受体刺激的树突状细胞上调TNFSF15和OX40L，诱导T辅助9应答和有效的抗肿瘤免疫。
Dectin-1 signalling in dendritic cells (DCs) has an important role in triggering protective antifungal Th17 responses. However, whether dectin-1 directs DCs to prime antitumour Th9 cells remains unclear. Here, we show that DCs activated by dectin-1 agonists potently promote naive CD4+ T cells to differentiate into Th9 cells. Abrogation of dectin-1 in DCs completely abolishes their Th9-polarizing capability in response to dectin-1 agonist curdlan. Notably, dectin-1 stimulation of DCs upregulates TNFSF15 and OX40L, which are essential for dectin-1-activated DC-induced Th9 cell priming. Mechanistically, dectin-1 activates Syk, Raf1 and NF-κB signalling pathways, resulting in increased p50 and RelB nuclear translocation and TNFSF15 and OX40L expression. Furthermore, immunization of tumour-bearing mice with dectin-1-activated DCs induces potent antitumour response that depends on Th9 cells and IL-9 induced by dectin-1-activated DCs in vivo. Our results identify dectin-1-activated DCs as a powerful inducer of Th9 cells and antitumour immunity and may have important clinical implications. Dendritic cells instruct different types of T cell responses depending on the types of microbial ligands sensed. Here the authors show that dendritic cells stimulated via Dectin-1 receptor upregulate TNFSF15 and OX40L and induce T helper 9 response and efficient antitumour immunity in mouse models.