Dendritic-cell maturation alters intracellular signaling networks, enabling differential effects of IFN-α/β on antigen cross-presentation
Dendritic-cell maturation alters intracellular signaling networks, enabling differential effects of IFN-α/β on antigen cross-presentation
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DOI：
10.1182/blood-2006-05-023465
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发表时间：
2007-02-01
期刊：
影响因子：
20.3
通讯作者：
Albert, Matthew L.
中科院分区：
文献类型：
--
作者：
Longman, Randy S.;Braun, Deborah;Albert, Matthew L.
I型干扰素（IFN）在先天性免疫和适应性免疫中的广泛且经常对比的作用被经由单个受体IFN-α受体（IFNAR）的信号传导所掩盖。在这里，我们表明，IFN-α/β诱导相反的影响，抗原交叉呈递的免疫结果取决于树突状细胞（DC）的成熟状态。尽管IFNAR表达相当，但未成熟的常规DC（cDC）响应于IFN-α/β激活STAT 1，而成熟DC暴露于IFN-α/β导致通过STAT 4的信号传导。微阵列分析揭示了由改变的信号传导引起的许多转录变化。重要的是，STAT 1信号传导导致CD 40 L诱导的IL-12产生的显著抑制，解释了CD 8（+）T细胞活化的抑制。这些数据为伴随DC成熟的信号通路中的分子开关提供了证据，该分子开关提供了DC调节来自周围环境的信号的整合的新机制。
The broad and often contrasting effects of type I interferons (IFNs) in innate and adaptive immunity are belied by the signaling via a single receptor, IFN-alpha receptor (IFNAR). Here, we show that IFN-alpha/beta induces opposing effects on the immunologic outcome of antigen cross-presentation depending on dendritic cell (DC) maturation status. Despite equivalent IFNAR expression, immature conven-tional DCs (cDCs) activate STAT1 in response to IFN-alpha/beta, whereas exposure of mature DCs to IFN-alpha/beta results in signaling via STAT4. Microarray analysis revealed numerous transcriptional changes resulting from the altered signaling. Importantly, STAT1 signaling resulted in significant inhibition of CD40L-induced IL-12 production, accounting for the inhibition of CD8(+) T-cell activation. These data provide evidence for a molecular switch in signaling pathways concomitant with DC maturation that offers a novel mechanism by which DCs modulate the integration of signals from the surrounding environment.