Downregulation of IL-13 gene transcription by T-bet in human T cells.

Background: Downregulation of a Th2 cytokine, IL-4, by a Th1-specific transcription factor, T-bet, has been demonstrated. However, the regulatory role of T-bet in another Th2 cytokine, IL-13, is not fully delineated.

Methods: IL-13 mRNA expression in Jurkat cells was examined by quantitative RT-PCR, while the transcriptional activity of 5'-flanking region in the IL-13 gene encompassing -1077 to +49 was investigated by fluorescence-based promoter reporter assay. The effect of T-bet was investigated by transfection of the cells with the T-bet expression vector.

Results: Stimulation with phorbol ester plus Ca2+ ionophore clearly induced IL-13 gene transcription in Jurkat cells. Ectopically expressed T-bet significantly suppressed the inducible mRNA expression and promoter activity of IL-13.

Conclusion: IL-13 expression was downregulated by T-bet at the level of gene transcription, independently of the modulation of Th1/Th2 balance. T-bet is the potential key factor in the development of Th1/Th2-related diseases.