title: Human gastric epithelial cells contribute to gastric immune regulation by providing retinoic acid to dendritic cells.
abstract: Despite the high prevalence of chronic gastritis caused by Helicobacter pylori, the gastric mucosa has received little investigative attention as a unique immune environment. Here, we analyzed whether retinoic acid (RA), an important homeostatic factor in the small intestinal mucosa, also contributes to gastric immune regulation. We report that human gastric tissue contains high levels of the RA precursor molecule retinol (ROL), and that gastric epithelial cells express both RA biosynthesis genes and RA response genes, indicative of active RA biosynthesis. Moreover, primary gastric epithelial cells cultured in the presence of ROL synthesized RA in vitro and induced RA biosynthesis in co-cultured monocytes through an RA-dependent mechanism, suggesting that gastric epithelial cells may also confer the ability to generate RA on gastric dendritic cells (DCs). Indeed, DCs purified from gastric mucosa had similar levels of aldehyde dehydrogenase activity and RA biosynthesis gene expression as small intestinal DCs, although gastric DCs lacked CD103. In H. pylori-infected gastric mucosa, gastric RA biosynthesis gene expression was severely disrupted, which may lead to reduced RA signaling and thus contribute to disease progression. Collectively, our results support a critical role for RA in human gastric immune regulation.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: D
authors.initials: D
authors.lastname: Bimczok
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, Michigan, USA.
authors.forename: J Y
authors.initials: JY
authors.lastname: Kao
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, Michigan, USA.
authors.forename: M
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: S
authors.initials: S
authors.lastname: Cochrun
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: P
authors.initials: P
authors.lastname: Mannon
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: S
authors.initials: S
authors.lastname: Peter
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Wilcox
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: K E
authors.initials: KE
authors.lastname: Mönkemüller
authors.affiliation: Department of Pediatrics, Gastroenterology and Nutrition, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: P R
authors.initials: PR
authors.lastname: Harris
authors.affiliation: Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Grams
authors.affiliation: Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Stahl
authors.affiliation: 1] Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA [2] VA Medical Center Research Service, Birmingham, Alabama, USA.
authors.forename: P D
authors.initials: PD
authors.lastname: Smith
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: L E
authors.initials: LE
authors.lastname: Smythies
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000276:immunology / Q000378:metabolism; D000818:Animals; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000276:immunology* / Q000382:microbiology; D005260:Female; D005753:Gastric Mucosa / Q000276:immunology* / Q000382:microbiology; D016481:Helicobacter Infections / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D018928:Immunity, Mucosal; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology / Q000382:microbiology; D061251:Primary Cell Culture; D014212:Tretinoin / Q000276:immunology* / Q000378:metabolism; D014801:Vitamin A / Q000276:immunology* / Q000378:metabolism
chemical_list: D014801:Vitamin A; D014212:Tretinoin; D000444:Aldehyde Dehydrogenase