title: Expression of retinaldehyde dehydrogenase enzymes in mucosal dendritic cells and gut-draining lymph node stromal cells is controlled by dietary vitamin A.
abstract: The vitamin A metabolite retinoic acid (RA) plays a crucial role in mucosal immune responses. We demonstrate in this study that RA-producing retinaldehyde dehydrogenase (RALDH) enzymes are postnatally induced in mesenteric lymph node (MLN) dendritic cells (DCs) and MLN stromal cells. RALDH enzyme activity in lamina propria-derived CD103(+) MLN-DCs did not depend on TLR signaling. Remarkably, RA itself could directly induce RALDH2 in both DCs and stromal cells in vitro. Furthermore, upon provision of a vitamin A-deficient diet, it was found that RA-mediated signaling was strongly reduced within the small intestines, while RALDH2 mRNA and RALDH enzyme activity in lamina propria DCs and MLN-DCs, as well as RALDH2 mRNA expression in MLN stromal cells, were strongly diminished. Moreover, supply of vitamin A to vitamin A-deficient mice restored RA-mediated signaling in the intestine and RALDH activity in lamina propria-derived CD103(+) MLN-DCs. Our results show that RA-dependent signaling within the intestine is indispensable for RALDH activity in the draining MLN.
authors.affiliation: Department of Molecular Cell Biology and Immunology, Vrije University Medical Center, 1007 MB Amsterdam, The Netherlands.
authors.forename: Rosalie
authors.initials: R
authors.lastname: Molenaar
authors.forename: Marlene
authors.initials: M
authors.lastname: Knippenberg
authors.forename: Gera
authors.initials: G
authors.lastname: Goverse
authors.forename: Brenda J
authors.initials: BJ
authors.lastname: Olivier
authors.forename: Alex F
authors.initials: AF
authors.lastname: de Vos
authors.forename: Tom
authors.initials: T
authors.lastname: O'Toole
authors.forename: Reina E
authors.initials: RE
authors.lastname: Mebius
mesh_terms: D000445:Aldehyde Oxidoreductases / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D000821:Animal Feed; D000818:Animals; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D005786:Gene Expression Regulation / Q000276:immunology*; D007413:Intestinal Mucosa / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D007421:Intestine, Small / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D008643:Mesentery / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D051379:Mice; D050697:Retinal Dehydrogenase / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D017154:Stromal Cells / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D014212:Tretinoin / Q000502:physiology*; D014801:Vitamin A / Q000008:administration & dosage / Q000502:physiology*; D014802:Vitamin A Deficiency / Q000201:enzymology / Q000276:immunology / Q000473:pathology
chemical_list: D014801:Vitamin A; D014212:Tretinoin; D000445:Aldehyde Oxidoreductases; C470579:RALDH2 protein, mouse; D050697:Retinal Dehydrogenase