Type I interferon inhibits expression of the alternative GATA3 transcript in human Th2 cells (57.22)

Abstract

Abstract The GATA3 transcription factor contributes to multiple immune processes, including the differentiation of T helper type 2 (Th2) cells. Th2 cells regulate many aspects of allergic disorders and express GATA3 in response to IL-4 signaling. Subsequently, GATA3 promotes transcription of the Th2 cytokines while also creating a feed-forward loop that stabilizes Th2 commitment. A previous study in mice has shown that Th2 commitment is accompanied by increased utilization of an alternate first exon (exon 1A) in the GATA3 transcript via an upstream promoter. The resulting transcript contains the same protein coding sequence but permits cell-specific control of expression levels. We previously demonstrated that the antiviral cytokine type I interferon (IFN-α/β) suppresses GATA3 mRNA and protein levels both in developing Th2 cells and in fully committed Th2 cells, leading to a decrease in Th2 cytokine expression. Here, we show that IL-4 significantly enhances utilization of exon 1A in the GATA3 transcripts in human Th2 cells. IFN-α/β preferentially inhibits expression of the exon 1A transcript, suggesting that IFN-α/β can regulate Th2 cells without affecting the basal levels of GATA3 required for other immune processes. Thus, IFN-α/β suppresses GATA3 in human Th2 cells and may be useful as a novel therapeutic for asthma and allergy.