BioProject

The transcription factor IRF8 is expressed in many types of blood cells and plays critical roles in cellular differentiation and function. More...

The transcription factor IRF8 is expressed in many types of blood cells and plays critical roles in cellular differentiation and function. However, the role of IRF8 in nonhematopoietic systems remains poorly understood. In this study, we examined the role of IRF8 in gastric epithelial cells (GECs) and provided evidence that IRF8 is a transcriptional modulator of the gastric mucosa necessary for limiting H. pylori colonization. H. pylori infection significantly upregulated expression of IRF8, which in turn promoted IFN-γ expression by GECs. Mice deficient of IRF8 exhibited increased H. pylori colonization and aborted induction of mucosal IFN-γ. Genome-wide analyses of IFN-γ-treated GECs by ChIP-seq and RNA-seq led to identification of IRF8 target genes with many belonging to the IFN regulated gene family that was previously observed in immune cells. Our results identify the IRF8- IFN-γ circuit as a previously unrecognized gastric innate immune mechanism in defense against infection of H. pylori. Overall design: Genome-wide transcription factors mapping and binding of IRF8 in mouse gastric epithelial cells (GECs). RNA-Seq is performed in mouse GECs, treated with or without IFN-γ. Less...