Inhibition of Th1 development mediated by GATA-3 through an IL-4-independent mechanism
Inhibition of Th1 development mediated by GATA-3 through an IL-4-independent mechanism
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DOI：
10.1016/s1074-7613(00)80671-8
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发表时间：
1998-11-01
期刊：
影响因子：
32.4
通讯作者：
Murphy, KM
中科院分区：
文献类型：
--
作者：
Ouyang, W;Ranganath, SH;Murphy, KM
最近，转录因子加塔-3显示出选择性地在Th 2细胞中表达，而不是在Th 1细胞中表达，并增加Th 2特异性细胞因子。在这里，我们表明，加塔-3表达的发展中的Th 1细胞的损失需要IL-12信号通过Stat 4，并不简单地导致从IL-4的缺乏。此外，我们证明了一个新的作用加塔-3直接抑制Th 1的发展不同的积极行动对Th 2-特异性细胞因子。加塔-3通过细胞内在机制抑制Th 1细胞因子，该机制不依赖于IL-4，并且可能涉及抑制IL-12信号传导。因此，加塔-3表达和IL-12信号传导是相互拮抗的，这有助于在早期Th发育期间一种途径的快速优势，产生细胞因子谱的稳定分歧。
Recently, the transcription factor GATA-3 was shown to be selectively expressed in Th2 but not Th1 cells and to augment Th2-specific cytokines. Here, we show that loss of GATA-3 expression by developing Th1 cells requires IL-12 signaling through Stat4 and does not simply result from an absence of IL-4. Moreover, we demonstrate a novel role for GATA-3 in directly repressing Th1 development distinct from its positive actions on Th2-specific cytokines. GATA-3 inhibits Th1 cytokines by a cell-intrinsic mechanism that is not dependent on IL-4 and that may involve repression of IL-12 signaling. Thus, GATA-3 expression and IL-12 signaling are mutually antagonistic, which facilitates rapid dominance of one pathway during early Th development, producing a stable divergence in cytokine profiles.