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  • Title: Inhibition of allergic inflammation in a murine model of asthma by expression of a dominant-negative mutant of GATA-3.
    Author: Zhang DH, Yang L, Cohn L, Parkyn L, Homer R, Ray P, Ray A.
    Journal: Immunity; 1999 Oct; 11(4):473-82. PubMed ID: 10549629.
    Abstract:
    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.
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