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.
Publication types
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Aerosols
-
Amino Acid Substitution
-
Animals
-
Asthma / chemically induced
-
Asthma / genetics
-
Asthma / immunology*
-
Asthma / pathology
-
Bronchoalveolar Lavage Fluid / immunology
-
DNA-Binding Proteins / genetics*
-
DNA-Binding Proteins / physiology
-
Drug Hypersensitivity / genetics
-
Drug Hypersensitivity / immunology
-
Drug Hypersensitivity / pathology
-
Eosinophilia / immunology
-
Eosinophilia / prevention & control
-
GATA3 Transcription Factor
-
Gene Expression Regulation
-
Genes, Dominant
-
Immunization
-
Immunoglobulin E / biosynthesis
-
Inflammation
-
Interleukin-13 / biosynthesis*
-
Interleukin-13 / genetics
-
Interleukin-4 / biosynthesis*
-
Interleukin-4 / genetics
-
Interleukin-5 / biosynthesis*
-
Interleukin-5 / genetics
-
Lung / immunology
-
Lung / pathology*
-
Mice
-
Mice, Inbred C57BL
-
Mice, Transgenic
-
Mucus / metabolism
-
Mutagenesis, Site-Directed
-
Ovalbumin / administration & dosage
-
Ovalbumin / immunology
-
Ovalbumin / toxicity
-
Th2 Cells / immunology*
-
Th2 Cells / metabolism
-
Trans-Activators / genetics*
-
Trans-Activators / physiology
Substances
-
Aerosols
-
DNA-Binding Proteins
-
GATA3 Transcription Factor
-
Gata3 protein, mouse
-
Interleukin-13
-
Interleukin-5
-
Trans-Activators
-
Interleukin-4
-
Immunoglobulin E
-
Ovalbumin