Selective loss of type I interferon-induced STAT4 activation caused by a minisatellite insertion in mouse STAT2
Selective loss of type I interferon-induced STAT4 activation caused by a minisatellite insertion in mouse STAT2
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DOI：
10.1038/76932
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发表时间：
2000-07-01
影响因子：
30.5
通讯作者：
Murphy, KM
中科院分区：
文献类型：
--
作者：
Farrar, JD;Smith, JD;Murphy, KM
使用鼠系统来模拟病原体诱导的人类疾病，假定这些物种AVE之间的一般免疫机制。一种重要的免疫调节机制涉及与先天和适应性免疫联系起来，以指导T Helper子集的发展，例如通过STAT4激活向子集I（Thi）发育。在分析I型干扰素信号传导中，我们发现了鼠和人类细胞之间的差异，这可能会影响这两个物种如何控制先天和适应性免疫之间的联系。我们表明，在人类中，I型干扰素会诱导Thi发育，并可以通过STAT2的羧基末端募集到IFN-Alpha受体复合物来激活STAT4。但是，小鼠STAT2基因具有一种微型插入，该插入改变了羧基末端，并有选择地破坏了激活STAT4的能力，但没有破坏其他统计数据。鼠STAT2中的这种缺陷表明，导致STAT4激活的信号和CD4（+）T细胞中THI发育的信号在小鼠和人之间有所不同。
The use of murine systems to model pathogen-induced human diseases presumes that general immune mechanisms between these species ave conserved. One important immunoregulatory mechanism involves linkage of innate and adaptive immunity to direct the development of T helper subsets, for example toward subset I (THI) development through STAT4 activation. In analyzing type I interferon signaling, we uncovered a difference between murine and human cells which may affect how these two species control linkage between innate and adaptive immunity. We show that in humans, type I interferons induce THI development and can activate STAT4 by recruitment to the IFN-alpha receptor complex specifically via the carboxy-terminus of STAT2. However, the mouse Stat2 gene harbors a minisatellite insertion that has altered the carboxy-terminus and selectively disrupted its capacity to activate STAT4, but not other STATs. This defect in murine Stat2 suggests that the signals leading to STAT4 activation and THI development in CD4(+)T cells are different between mice and humans.