Inhibition of allergic inflammation in a murine model of asthma by expression of a dominant-negative mutant of GATA-3.
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.
Zhang
D H
DH
Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Yang
L
L
Cohn
L
L
Parkyn
L
L
Homer
R
R
Ray
P
P
Ray
A
A
D000336:Aerosols; D019943:Amino Acid Substitution; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D004342:Drug Hypersensitivity / Q000235:genetics / Q000276:immunology / Q000473:pathology; D004802:Eosinophilia / Q000276:immunology / Q000517:prevention & control; D050990:GATA3 Transcription Factor; D005786:Gene Expression Regulation; D005799:Genes, Dominant; D007114:Immunization; D007073:Immunoglobulin E / Q000096:biosynthesis; D007249:Inflammation; D018793:Interleukin-13 / Q000096:biosynthesis* / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics; D015848:Interleukin-5 / Q000096:biosynthesis* / Q000235:genetics; D008168:Lung / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009093:Mucus / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000502:physiology
D000336:Aerosols; D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D018793:Interleukin-13; D015848:Interleukin-5; D015534:Trans-Activators; D015847:Interleukin-4; D007073:Immunoglobulin E; D010047:Ovalbumin