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 asso
ciated with this disease. Recently, the transcription factor GATA-3 was sho
wn 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 col
ocalization within the airways of asthmatic and nonasthmatic individuals.
Methods: We investigated the association between GATA-3 gene expression, ai
rway inflammatory cells, and IL-5 gene expression in bronchoalveolar lavage
fluid and bronchial biopsy specimens from atopic asthmatic subjects (n = 1
0) and normal control subjects (n = 10).
Results: We report that GATA-3 mRNA expression is significantly increased i
n the airways of asthmatic subjects compared with those of normal control s
ubjects (P < .001). Numbers of cells expressing GATA-3 transcripts correlat
ed significantly with reduced airway caliber (P < .05) and airways hyperres
ponsiveness (P < .05) in asthmatic subjects. Colocalization studies showed
that the majority (approximately 60% to 90%) of GATA-3 mRNA(+) cells in ast
hmatic airways were CD3(+) T cells, with smaller contributions from major b
asic protein(+) eosinophils and tryptase(+) mast cells. The density of GATA
-3 mRNA+ cells correlated significantly with the numbers of cells expressin
g 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 increas
ed GATA-3 gene expression in association with IL-5 mRNA+ cells in asthmatic
airways. These findings support a causal association between augmented GAT
A-3 expression and dysregulated IL-5 expression in atopic asthma.