Inhibition of allergic inflammation in a murine model of asthma by expression of a dominant-negative mutant of GATA-3

被引:287
作者
Zhang, DH
Yang, LY
Cohn, L
Parkyn, L
Homer, R
Ray, P
Ray, A [1 ]
机构
[1] Yale Univ, Sch Med, Dept Med, Pulm & Crit Care Sect, New Haven, CT 06520 USA
[2] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA
[3] Vet Adm Connecticut Healthcare Syst, Pathol & Lab Med Serv, West Haven, CT 06516 USA
关键词
D O I
10.1016/S1074-7613(00)80122-3
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:473 / 482
页数:10
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