Selective contribution of IFN-α/β signaling to the maturation of dendritic cells induced by double-stranded RNA or viral infection

Selective contribution of IFN-α/β signaling to the maturation of dendritic cells induced by double-stranded RNA or viral infection
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DOI:
10.1073/pnas.1934678100
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发表时间:
2003-09-16
影响因子:
11.1
通讯作者:
Taniguchi, T
Taniguchi, T
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Honda, K;Sakaguchi, S;Taniguchi, T

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树突状细胞(DC)成熟可能有一个复杂的机制,其中toll样受体和其他信号通路可能根据病原体的性质进行不同的协调,以使DC成熟对给定的威胁最有效。本研究表明,体外双链RNA或病毒感染诱导的dc成熟选择性地需要ifn - α / β信号。有趣的是,在缺乏ifn - α / β的两个靶基因TLR3和PKR(双链rna依赖性蛋白激酶R)中的任何一个的情况下,成熟仍然被观察到,这表明ifn - α / β诱导的dc转录程序的复杂性。我们还发现,这些药物在体内刺激的dc可以迁移到脾脏的T细胞区,但在没有IFN信号的情况下不能成熟。免疫系统可能已经获得了这种细胞因子系统的选择性利用,它是先天抗病毒免疫所必需的,可以有效地与适应性免疫的诱导相结合。
A complex mechanism may be operational for dendritic cell (DC) maturation, wherein Toll-like receptor and other signaling pathways may be coordinated differently depending on the nature of the pathogens, in order for DC maturation to be most effective to a given threat. Here, we show that IFN-alpha/beta signaling is selectively required for the maturation of DCs induced by double-stranded RNA or viral infection in vitro. Interestingly, the maturation is still observed in the absence of either of the two target genes of IFN-alpha/beta, TLR3 and PKR (double-stranded-RNA-dependent protein kinase R), indicating the complexity of the IFN-alpha/beta-induced transcriptional program in DCs. We also show that the DCs stimulated in vivo by these agents can migrate into the T cell zone of the spleen but fail to mature without the IFN signal. The immune system may have acquired the selective utilization of this cytokine system, which is essential for innate antiviral immunity, to effectively couple with the induction of adaptive immunity.