Gene expression of the GATA-3 transcription factor is increased in atopic asthma

Background: High expression of IL-5 by T cells in the airways of asthmatic individuals is believed to play a fundamental role in the eosinophilia associated with this disease. Recently, the transcription factor GATA-3 was shown to be critical for IL-5 gene expression in T-H2 cells in vitro. Objective: Our aim was to examine the expression of GATA-3 mRNA and its colocalization within the airways of asthmatic and nonasthmatic individuals. Methods: We investigated the association between GATA-3 gene expression, airway inflammatory cells, and IL-5 gene expression in bronchoalveolar lavage fluid and bronchial biopsy specimens from atopic asthmatic subjects (n = 10) and normal control subjects (n = 10). Results: We report that GATA-3 mRNA expression is significantly increased in the airways of asthmatic subjects compared with those of normal control subjects (P < .001). Numbers of cells expressing GATA-3 transcripts correlated significantly with reduced airway caliber (P < .05) and airways hyperresponsiveness (P < .05) in asthmatic subjects. Colocalization studies showed that the majority (approximately 60% to 90%) of GATA-3 mRNA(+) cells in asthmatic airways were CD3(+) T cells, with smaller contributions from major basic protein(+) eosinophils and tryptase(+) mast cells. The density of GATA-3 mRNA+ cells correlated significantly with the numbers of cells expressing IL-5 mRNA (P < .001, r = 0.879 for bronchoalveolar lavage fluid; P < .05, r = 0.721 for biopsy specimens). Furthermore, double in situ hybridization demonstrated that approximately 76% of GATA-3 mRNA(+) cells coexpressed IL-5 mRNA and that 91% of IL-5 mRNA(+) cells coexpressed GATA-3 mRNA. Conclusion: The results of this study provide the first evidence of increased GATA-3 gene expression in association with IL-5 mRNA+ cells in asthmatic airways. These findings support a causal association between augmented GATA-3 expression and dysregulated IL-5 expression in atopic asthma.