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Publication : Cutting Edge: Expression of IRF8 in Gastric Epithelial Cells Confers Protective Innate Immunity against Helicobacter pylori Infection.

First Author  Yan M Year  2016
Journal  J Immunol Volume  196
Issue  5 Pages  1999-2003
PubMed ID  26843324 Mgi Jnum  J:331034
Mgi Id  MGI:6871223 Doi  10.4049/jimmunol.1500766
Citation  Yan M, et al. (2016) Cutting Edge: Expression of IRF8 in Gastric Epithelial Cells Confers Protective Innate Immunity against Helicobacter pylori Infection. J Immunol 196(5):1999-2003
abstractText  IFN regulatory factor 8 (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 provide evidence that IRF8 is a transcriptional modulator of the gastric mucosa necessary for limiting Helicobacter pylori colonization. H. pylori infection significantly upregulated expression of IRF8, which, in turn, promoted IFN-gamma expression by gastric epithelial cells. Mice deficient in IRF8 exhibited increased H. pylori colonization and aborted induction of mucosal IFN-gamma. Genome-wide analyses of IFN-gamma-treated gastric epithelial cells by chromatin immunoprecipitation sequencing and RNA sequencing led to the identification of IRF8 target genes, with many belonging to the IFN-regulated gene family that was observed previously in immune cells. Our results identify the IRF8-IFN-gamma circuit as a novel gastric innate immune mechanism in the host defense against infection with H. pylori.
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