title: Cutting Edge: Expression of IRF8 in Gastric Epithelial Cells Confers Protective Innate Immunity against Helicobacter pylori Infection.
abstract: 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-γ expression by gastric epithelial cells. Mice deficient in IRF8 exhibited increased H. pylori colonization and aborted induction of mucosal IFN-γ. Genome-wide analyses of IFN-γ-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-γ circuit as a novel gastric innate immune mechanism in the host defense against infection with H. pylori.
authors: Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892; hmorse@niaid.nih.gov wanghongs@niaid.nih.gov yanming@mail.nih.gov.
authors: Ming
authors: M
authors: Yan
authors: Virology and Cellular Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852; hmorse@niaid.nih.gov wanghongs@niaid.nih.gov yanming@mail.nih.gov.
authors: Hongsheng
authors: H
authors: Wang
authors: Virology and Cellular Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852;
authors: Jiafang
authors: J
authors: Sun
authors: Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892; Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892; and.
authors: Wei
authors: W
authors: Liao
authors: Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892; Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892; and.
authors: Peng
authors: P
authors: Li
authors: Department of Gastroenterology, First Affiliated Hospital, Nanchang University, Nanchang 330006, China.
authors: Yin
authors: Y
authors: Zhu
authors: Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892;
authors: Chengfu
authors: C
authors: Xu
authors: Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892;
authors: Jungsoo
authors: J
authors: Joo
authors: Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892;
authors: Yan
authors: Y
authors: Sun
authors: Virology and Cellular Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852;
authors: Sadia
authors: http://orcid.org/0000-0002-8292-6813
authors: S
authors: Abbasi
authors: Virology and Cellular Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852;
authors: Alexander
authors: A
authors: Kovalchuk
authors: Department of Gastroenterology, First Affiliated Hospital, Nanchang University, Nanchang 330006, China.
authors: Nonghua
authors: N
authors: Lv
authors: Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892; Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892; and.
authors: Warren J
authors: WJ
authors: Leonard
authors: Virology and Cellular Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852; hmorse@niaid.nih.gov wanghongs@niaid.nih.gov yanming@mail.nih.gov.
authors: Herbert C
authors: http://orcid.org/0000-0002-9331-3705
authors: HC
authors: Morse
mesh_terms: D000818:Animals; D015153:Blotting, Western; D047369:Chromatin Immunoprecipitation; D005434:Flow Cytometry; D005753:Gastric Mucosa / Q000276:immunology* / Q000382:microbiology*; D005786:Gene Expression Regulation / Q000276:immunology*; D016481:Helicobacter Infections / Q000276:immunology*; D016480:Helicobacter pylori; D007113:Immunity, Innate / Q000276:immunology*; D007150:Immunohistochemistry; D050835:Interferon Regulatory Factors / Q000096:biosynthesis / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D000099185:Interferon Regulatory Factor-8
chemical_list: D050835:Interferon Regulatory Factors; D007371:Interferon-gamma; D000099185:Interferon Regulatory Factor-8