The cell type-specific expression of the murine IL-13 gene is regulated byGATA-3

IL-13, a Th2 cell-specific cytokine, is a major effector molecule mediating several pathological features of allergic asthma. However, the transcripti onal 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 add ition, 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 1L-13 promoter is mediated by a functionally critical GATA-3 site that hin ds endogenous GATA-3 proteins, whereas the induction by PMA/ionomycin is me diated by distinct cis-acting elements. Furthermore, by expressing GATA-3 i n wild-type and c-maf transgenic Th1 cells, we demonstrate that the express ion 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 d oes not have to be mutually exclusive in effector Th cells.