Different GATA factors dictate CCR3 transcription in a cell type-specific manner of allergic inflammatory cells

Abstract

CCR3 is expressed in prominent allergic inflammatory cells, including eosinophils, mast cells, and Th2 cells, which preferentially express GATA-1, GATA-2, and GATA-3, respectively. We have previously demonstrated GATA-1-mediated CCR3 transcription with functional mapping of a GATA element in the regulatory region of CCR3 gene. Herein, we investigated whether GATA factors other than GATA-1 play a major role in CCR3 transcription in these cell types. A CCR3 reporter plasmid, but not a mutant CCR3 reporter lacking the functional GATA element, was activated in all three cell types, EoL-1 eosinophilic cells, HMC-1 master cells, and Jurkat T cells, suggesting a critical involvement of the GATA element regardless of cell types expressing different GATA factors. Knockdown assay showed that siRNAs directed to GATA-1 and GATA-2 significantly reduced CCR3 transactivation with an additive effect in EoL-1 and HMC-1 cells, while GATA-3 siRNA exclusively abrogated CCR3 transcription in Jurkat cells. In parallel, EMSA analysis showed that the functional GATA element preferentially bound GATA-1, GATA-2, and GATA-3 with nuclear extracts from EoL-1, HMC-1, and Jurkat T cells, respectively. These results highlight that different GATA factors are engaged in CCR3 transcription in a cell type-specific fashion, depending on the major allergic inflammatory cells.