The role of GATA2 in the expression of the soluble decoy receptor ST2/IL1RL1 in human and mouse mast cells

The ST2/IL1RL1 gene encodes a receptor subunit for IL-33. The ST2/IL1RL1 gene is transcribed and translated to two splice variants, full-length ST2 (ST2L) and soluble ST2 (sST2). ST2L is expressed on cell surface as membrane bound molecule and forms a heterodimer with IL-1RAcP, which plays an important role in Th2 transduces a signaling of IL-33. In contrast, sST2 blocks the IL-33-signaling via functioning as a decoy receptor of IL-33. In this study, we analyzed the regulatory mechanisms of the gene expression of sST2 in mast cell, the major source of sST2. We found that a hematopoietic cell-specific transcription factor GATA2 is essential for sST2 expression in human mast cells (a cell line and primary cells) and mouse mast cells. Various assays including ChIP assay, reporter assay, and 3C assay revealed that GATA2 binding to the distal promoter of the IL1RL1 gene transcriptionally activates proximal promoter-driven expression of sST2 through chromosomal conformation.