The cell type-specific expression of the murine IL-13 gene is regulated by GATA-3.
IL-13, a Th2 cell-specific cytokine, is a major effector molecule mediating several pathological features of allergic asthma. However, the transcriptional regulation of the IL-13 gene remains unclear. Here we demonstrate, by using intracellular cytokine staining, that IL-13 is not always coexpressed with other Th2 cytokines in normal Th cells on a single cell basis. In addition, we identified and cloned a minimal inducible and cell type-specific promoter of the murine IL-13 gene. The cell type specificity of the minimal IL-13 promoter is mediated by a functionally critical GATA-3 site that binds endogenous GATA-3 proteins, whereas the induction by PMA/ionomycin is mediated by distinct cis-acting elements. Furthermore, by expressing GATA-3 in wild-type and c-maf transgenic Th1 cells, we demonstrate that the expression of IL-13 is regulated by a mechanism distinct from that regulating the expression of IL-4, and that the expression of Th1 and Th2 cytokine genes does not have to be mutually exclusive in effector Th cells.
Kishikawa
H
H
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Harvard Medical School, Boston, MA 02115, USA.
Sun
J
J
Choi
A
A
Miaw
S C
SC
Ho
I C
IC
D000818:Animals; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000378:metabolism*; D050990:GATA3 Transcription Factor; D018793:Interleukin-13 / Q000235:genetics*; D051379:Mice; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051257:Proto-Oncogene Proteins c-maf; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D014018:Tissue Distribution; D015534:Trans-Activators / Q000378:metabolism*; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D018793:Interleukin-13; C495608:Maf protein, mouse; D011518:Proto-Oncogene Proteins; D051257:Proto-Oncogene Proteins c-maf; D015534:Trans-Activators