Stat6-independent GATA-3 autoactivation directs IL-4-independent Th2 development and commitment
Stat6-independent GATA-3 autoactivation directs IL-4-independent Th2 development and commitment
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DOI：
10.1016/s1074-7613(00)80156-9
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发表时间：
2000-01-01
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, WJ;Löhning, M;Murphy, KM
IL-4诱导Th2形成的最初来源和稳定Th2承诺的机制仍不清楚。我们发现Stat6缺陷的T细胞产生IL-4的减少水平明显高于Th1对照组。利用一种新的细胞表面亲和力矩阵技术，我们发现分泌IL-4的Stat6缺陷T细胞稳定表达GATA-3和Th2表型。将GATA-3导入STAT6缺陷的T细胞，可完全恢复Th2的发育，诱导c-Maf、IL-4基因上Th2特异的DNase I超敏部位和Th2细胞因子的表达。GATA-3在Stat6缺乏的T细胞中完全重建Th2发育的事实表明，它是Th2发育的主开关。最后，GATA-3发挥STAT6非依赖性的自激活作用，创建一个稳定Th2承诺的反馈途径。
The initial source of IL-4-inducing Th2 development and the mechanism of stable Th2 commitment remain obscure. We found the reduced level of IL-4 production in Stat6-deficient T cells to be significantly higher than in Th1 controls. Using a novel cell surface affinity matrix technique, we found that IL-4-secreting Stat6-deficient T cells stably expressed GATA-3 and Th2 phenotype. Introducing GATA-3 into Stat6-deficient T cells completely restored Th2 development, inducing c-Maf, Th2-specific DNase I hypersensitive sites in the IL-4 locus, and Th2 cytokine expression. The fact that GATA-3 fully reconstitutes Th2 development in Stat6-deficient T cells indicates it is a master switch in Th2 development. Finally, GATA-3 exerts Stat6-independent autoactivation, creating a feedback pathway stabilizing Th2 commitment.