Interleukin 12 signaling in T helper type 1 (Th1) cells involves tyrosine phosphorylation of signal transducer and activator of transcription (Stat)3 and Stat4.
Interleukin 12 signaling in T helper type 1 (Th1) cells involves tyrosine phosphorylation of signal transducer and activator of transcription (Stat)3 and Stat4.
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DOI：
10.1084/jem.181.5.1755
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发表时间：
1995-05-01
期刊：
影响因子：
--
通讯作者：
Murphy KM
中科院分区：
文献类型：
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作者：
Jacobson NG;Szabo SJ;Weber-Nordt RM;Zhong Z;Schreiber RD;Darnell JE Jr;Murphy KM
白细胞介素12（IL - 12）启动初始CD4 + T细胞向1型辅助性T细胞（Th1）分化，这对抵抗诸如硕大利什曼原虫等胞内病原体至关重要。为了探究IL - 12作用的基础，我们分析了Th1细胞中核因子的诱导情况。IL - 12选择性地诱导包含Stat3和Stat4的核DNA结合复合物，Stat3和Stat4是最近克隆出的信号转导子和转录激活子（STATs）家族成员。虽然Stat3参与几种其他细胞因子的信号传导，但此前并不知道Stat4参与任何天然配体的信号通路。Stat4的选择性激活为IL - 12在Th1细胞发育中的独特作用提供了基础。因此，本研究首次确定了T细胞中IL - 12信号传导的早期事件以及Stat4的配体激活。
Interleukin 12 (IL-12) initiates the differentiation of naive CD4+ T cells to T helper type 1 (Th1) cells critical for resistance to intracellular pathogens such as Leishmania major. To explore the basis of IL-12 action, we analyzed induction of nuclear factors in Th1 cells. IL-12 selectively induced nuclear DNA-binding complexes that contained Stat3 and Stat4, recently cloned members of the family of signal transducers and activators of transcription (STATs). While Stat3 participates in signaling for several other cytokines, Stat4 was not previously known to participate in the signaling pathway for any natural ligand. The selective activation of Stat4 provides a basis for unique actions of IL-12 on Th1 development. Thus, this study presents the first identification of the early events in IL-12 signaling in T cells and of ligand activation of Stat4.