The Ets transcription factor ERM is Th1-specific and induced by IL-12 through a Stat4-dependent pathway
The Ets transcription factor ERM is Th1-specific and induced by IL-12 through a Stat4-dependent pathway
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DOI：
10.1073/pnas.96.7.3888
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发表时间：
1999-03-30
影响因子：
11.1
通讯作者：
Murphy, KM
中科院分区：
文献类型：
--
作者：
Ouyang, W;Jacobson, NG;Murphy, KM
白细胞介素12 （IL-12）诱导的辅助性T细胞1 （Th1）发育需要Stat4激活。然而，抗原激活的Th1细胞可以独立于IL-12和Stat4激活产生干扰素γ (ifn - γ)。因此，在分化的Th1细胞中，受IL-12和Stat4调控的因子可能参与ifn - γ的产生。通过减法克隆，我们确定了ERM，一个Ets转录因子，是th1特异性的，il -12诱导的基因。il -12诱导的ERM发生在野生型和stat1缺失的T细胞中，而不是stat4缺失的T细胞中，这表明ERM是stat4诱导的。逆转录病毒表达的ERM不能恢复缺乏stat4的T细胞中ifn - γ的产生，但增加了stat4杂合T细胞中ifn - γ的表达。Ets因子经常通过与其他转录因子的合作相互作用来调节转录，据报道ERM与c-Jun合作。然而，在缺乏其他转录因子的情况下，ERM仅将IFN-y报告因子的表达增强了2倍。因此，确定Th1发育过程中ERM的需求可能需要基因靶向。
Interleukin 12 (IL-12)-induced T helper 1 (Th1) development requires Stat4 activation. However, antigen-activated Th1 cells can produce interferon gamma (IFN-gamma) independently of IL-12 and Stat4 activation. Thus, in differentiated Th1 cells, factors regulated by IL-12 and Stat4 may be involved in IFN-gamma production. Using subtractive cloning, we identified ERM, an Ets transcription factor, to be a Th1-specific, IL-12-induced gene. IL-12-induction of ERM occurred in wild-type and Stat1-deficient, but not Stat4-deficient, T cells, suggesting ERM is Stat4-inducible. Retroviral expression of ERM did not restore IFN-gamma production in Stat4-deficient T cells, but augmented IFN-gamma expression in Stat4-heterozygous T cells. Ets factors frequently regulate transcription via cooperative interactions with other transcription factors, and ERM has been reported to cooperate with c-Jun, However, in the absence of other transcription factors, ERM augmented expression of an IFN-y reporter by only 2-fold. Thus, determining the requirement for ERM in Th1 development likely will require gene targeting.