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

The cytokines IL-4, IL-5, and IL-13, secreted by Th2 cells, have distinct f unctions in the pathogenesis of asthma. We have previously shown that the t ranscription 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-spe cific 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 synthesi s, all key features of asthma, were severely attenuated in the transgenic m ice. Thus, targeting GATA-3 activity alone is sufficient to blunt Th2 respo nses in vivo, thereby establishing GATA-3 as a potential therapeutic target in the treatment of asthma and allergic diseases.