Requirement for Stat4 in interleukin-12-mediated responses of natural killer and T cells
Requirement for Stat4 in interleukin-12-mediated responses of natural killer and T cells
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DOI：
10.1038/382171a0
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发表时间：
1996-07-11
期刊：
影响因子：
64.8
通讯作者：
Ihle, JN
中科院分区：
文献类型：
--
作者：
Thierfelder, WE;vanDeursen, JM;Ihle, JN
信号转导子和转录激活子（STAT）在细胞因子的作用下被酪氨酸磷酸化激活，并介导其许多功能反应（1-3）。Statil最初是由于其与Stat 1的同源性而被克隆的（参考文献4，5），并且被广泛表达，尽管它在用白细胞介素（IL）-12刺激T细胞后仅被酪氨酸磷酸化（参考文献6，7）。IL-12是T细胞非依赖性诱导细胞因子干扰素（IFN）-γ所必需的，这是细菌和寄生虫感染最初抑制中的一个小桶步骤。IL-12对Th 1应答的发展也很重要，这对于有效的宿主防御细胞内病原体至关重要（8，9）。为了确定Stat 4的功能及其在IL-12信号传导中的作用，我们通过基因靶向产生了缺乏Stat 4的小鼠。小鼠存活且可生育，没有可检测到的造血缺陷，然而，测试的所有IL-12功能被破坏，包括IFN-γ的诱导、有丝分裂发生、自然杀伤细胞溶解功能的增强和Th 1分化。
SIGNAL transducers and activators of transcription (STATs) are activated by tyrosine phosphorylation in response to cytokines and mediate many of their functional responses(1-3). Statil was initially cloned as a result of its homology with Stat1 (refs 4, 5) and is widely expressed, although it is only tyrosine-phosphorylated after stimulation of T cells with interleukin (IL)-12 (refs 6, 7). IL-12 is required for the T-cell-independent induction of the cytokine interferon (IFN)-gamma, a keg step in the initial suppression of bacterial and parasitic infections. IL-12 is also important for the development of a Th1 response, which is critical for effective host defence against intracellular pathogens(8,9). To determine the function of Stat4 and its role in IL-12 signalling, we have produced mice that lack Stat4 by gene targeting. The mice were viable and fertile, with no detectable defects in haematopoiesis, However, all IL-12 functions tested were disrupted, including the induction of IFN-gamma, mitogenesis, enhancement of natural killer cytolytic function and Th1 differentiation.