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Immunity. 1999 Oct;11(4):473-82.

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

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1
Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.

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.

PMID:
10549629
DOI:
10.1016/s1074-7613(00)80122-3
[Indexed for MEDLINE]
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