Expression of retinaldehyde dehydrogenase enzymes in mucosal dendritic cells and gut-draining lymph node stromal cells is controlled by dietary vitamin A

• Published in: The Journal of immunology (1950) Vol. 186; no. 4; pp. 1934 - 1942
• Main Authors: Molenaar, Rosalie, Knippenberg, Marlene, Goverse, Gera, Olivier, Brenda J, de Vos, Alex F, O'Toole, Tom, Mebius, Reina E
• Format: Journal Article
• Language: English
• Published: United States 15.02.2011
• Subjects: Aldehyde Oxidoreductases - biosynthesis; Aldehyde Oxidoreductases - genetics; Aldehyde Oxidoreductases - physiology; Animal Feed; Animals; Dendritic Cells - enzymology; Dendritic Cells - immunology; Dendritic Cells - pathology; Gene Expression Regulation - immunology; Intestinal Mucosa - enzymology; Intestinal Mucosa - immunology; Intestinal Mucosa - pathology; Intestine, Small - enzymology; Intestine, Small - immunology; Intestine, Small - pathology; Lymph Nodes - enzymology; Lymph Nodes - immunology; Lymph Nodes - pathology; Mesentery - enzymology; Mesentery - immunology; Mesentery - pathology; Mice; Retinal Dehydrogenase - biosynthesis; Retinal Dehydrogenase - genetics; Retinal Dehydrogenase - physiology; Stromal Cells - enzymology; Stromal Cells - immunology; Stromal Cells - pathology; Tretinoin - physiology; Vitamin A - administration & dosage; Vitamin A - physiology; Vitamin A Deficiency - enzymology; Vitamin A Deficiency - immunology; Vitamin A Deficiency - pathology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1001672

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.