Negative regulation of IFN-α/β signaling by IFN regulatory factor 2 for homeostatic development of dendritic cells
Negative regulation of IFN-α/β signaling by IFN regulatory factor 2 for homeostatic development of dendritic cells
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DOI：
10.1073/pnas.0307336101
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发表时间：
2004-02-24
影响因子：
11.1
通讯作者：
Taniguchi, T
中科院分区：
文献类型：
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作者：
Honda, K;Mizutani, T;Taniguchi, T
抗原呈递细胞的不同亚群，特别是树突状细胞（dc）的发育和合作，可能对维持稳态免疫反应至关重要。最近，在DC激活的背景下，ifn - α / β，即病毒感染或toll样受体激活所诱导的细胞因子，受到了广泛的关注。在这里，我们发现缺乏IFN调节因子2的小鼠表现出cd8 α (-) dc的选择性损失，即所谓的髓系dc，这伴随着CD11c-CD11b（高）其他髓系细胞的显着增加。这种缺乏症是骨骼固有的。骨髓前体，其中IFN- α / β基因的异常诱导导致过度的IFN信号传导。IFN调节因子2在IFN- α / β信号的负调控中的关键功能被观察到通过引入IFN受体复合物的额外零突变来挽救缺陷，从而强调了IFN调节因子2的负调控功能。鉴于ifn - α / β信号在DC激活中的关键作用的证据越来越多，我们目前的研究提供了一个独特的例子，在DC的分化和激活过程中，细胞因子信号的大小应该以特定阶段的方式适当平衡。
The development and cooperation of distinct subsets of antigen-presenting cells, particularly dendritic cells (DCs), may be critical for maintaining homeostatic immune responses. Recently, much attention has been focused on IFN-alpha/beta, the cytokines induced en masse by virus infection or the activation of Toll-like receptors, in the context of DC activation. Here, we show that mice deficient in IFN regulatory factor 2 exhibit selective loss of CD8alpha(-) DCs, the so-called myeloid DCs, which is accompanied by a notable increase in CD11c-CD11b(high) other myeloid lineage cells. Such deficiency is intrinsic to the bone. marrow precursors, in which the abnormal induction of IFN-alpha/beta genes causes excessive IFN signaling. The critical function of IFN regulatory factor 2 in the negative regulation of IFN-alpha/beta signaling is underscored by the observation that the deficiency is rescued by introducing an additional null mutation for the IFN receptor complex. In view of accumulating evidence of the critical role of IFN-alpha/beta signaling in DC activation, our present study offers a unique example in that the magnitude of a cytokine signal should be properly balanced in a stage-specific manner during the differentiation and activation of DCs.