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Structure and Specificity of GATA Proteins in Th2 Development

机译：Th2发育中GATA蛋白的结构和特异性

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Development of Th2 subset of CD4+ T cells involves the interleukin-4 (IL-4)- and Stat6-dependent increase in GATA-3 expression during primary activation. Recently we reported that the phenotypic stability and factor independence of Th2 cells involves acquisition of an intracellular pathway that maintains GATA-3 expression. Evidence from retroviral expression studies implied that this pathway involved an autoactivation of GATA-3 expression, since Stat6-deficient T cells induced endogenous GATA-3 when infected with GATA-3-expressing retroviruses. That study left unresolved the issue of whether GATA-3 autoactivation was direct or indirect. Several other Th2-specific transcription factors have been described, including c-Maf and JunB. We therefore examined the ability of these other transcription factors to induce GATA-3 expression and promote Th2 development. Neither c-Maf nor JunB induced Th2 development in Stat6-deficient CD4+ T cells, in contrast to GATA-3. Consistent with this indication of a possible direct autoactivation pathway, we also observed that heterologous GATA family proteins GATA-1, GATA-2, and GATA-4 were also capable of inducing GATA-3 expression in developing Stat6-deficient T cells and promote Th2 development. Mutational analysis revealed evidence for two distinct mechanisms of GATA-3 action. IL-4 induction by GATA-3 required each of the functional domains to be present, whereas repression of gamma interferon could occur even when mutants of GATA-3 lacking the second transactivation domain, TA2, were expressed. The GATA-dependent induction of the GATA-3 but not the other GATA genes in T cells suggests that T-cell-specific cis elements within the GATA-3 locus likely cooperate with a general GATA recognition motif to allow GATA-3-dependent autoactivation.
机译：CD4 + T细胞Th2子集的发育涉及在初次激活过程中GATA-3表达中白介素4（IL-4）和Stat6依赖性增加。最近，我们报道了Th2细胞的表型稳定性和因子独立性涉及维持GATA-3表达的细胞内途径的获得。逆转录病毒表达研究的证据表明该途径涉及GATA-3表达的自动激活，因为当感染表达GATA-3的逆转录病毒时，Stat6缺陷型T细胞诱导内源性GATA-3。该研究尚未解决GATA-3自动激活是直接还是间接的问题。已经描述了几种其他的Th2特异性转录因子，包括c-Maf和JunB。因此，我们检查了这些其他转录因子诱导GATA-3表达并促进Th2发育的能力。与GATA-3相比，c-Maf和JunB均未在Stat6缺失的CD4 + T细胞中诱导Th2发育。与可能的直接自激活途径的这种指示一致，我们还观察到异源GATA家族蛋白GATA-1，GATA-2和GATA-4也能够在发育中的Stat6缺陷T细胞中诱导GATA-3表达并促进Th2发展。突变分析揭示了两种不同的GATA-3作用机制的证据。通过GATA-3诱导IL-4需要存在每个功能域，而即使表达了缺少第二个反式激活域TA2的GATA-3突变体，也可能发生γ干扰素的抑制。 GATA-3而非GATA基因在T细胞中的GATA依赖性诱导表明，GATA-3基因座中T细胞特异的 cis 元件可能与一般的GATA识别基序协同作用允许依赖GATA-3的自动激活。

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