Inhibition of allergic inflammation in a murine model of asthma by expression of a dominant-negative mutant of GATA-3
Inhibition of allergic inflammation in a murine model of asthma by expression of a dominant-negative mutant of GATA-3
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DOI：
10.1016/s1074-7613(00)80122-3
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发表时间：
1999-10-01
期刊：
影响因子：
32.4
通讯作者：
Ray, A
中科院分区：
文献类型：
--
作者：
Zhang, DH;Yang, LY;Ray, A
由Th2细胞分泌的细胞因子IL-4、IL-5和IL-13在哮喘的发病机制中具有不同的作用。我们之前已经证明转录因子GATA-3在Th2细胞中表达，但不在Th1细胞中表达。然而，目前尚不清楚GATA-3是否控制了所有Th2细胞因子的表达。在小鼠体内以T细胞特异性方式表达显性-负性GATA-3突变体导致所有Th2细胞因子IL-4、IL-5和IL-13水平降低。在转基因小鼠中，哮喘的关键特征--呼吸道嗜酸性粒细胞增多、粘液产生和IgE合成--都严重减弱。因此，仅靶向GATA-3活性就足以钝化体内Th2反应，从而使GATA-3成为治疗哮喘和过敏性疾病的潜在治疗靶点。
The cytokines IL-4, IL-5, and IL-13, secreted by Th2 cells, have distinct functions in the pathogenesis of asthma. We have previously shown that the transcription factor GATA-3 is expressed in Th2 but not Th1 cells. However, it was unclear whether GATA-3 controls the expression of all Th2 cytokines. Expression of a dominant-negative mutant of GATA-3 in mice in a T cell-specific fashion led to a reduction in the levels of all the Th2 cytokines IL-4, IL-5, and IL-13. Airway eosinophilia, mucus production, and IgE synthesis, all key features of asthma, were severely attenuated in the transgenic mice. Thus, targeting GATA-3 activity alone is sufficient to blunt Th2 responses in vivo, thereby establishing GATA-3 as a potential therapeutic target in the treatment of asthma and allergic diseases.