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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aldehyde Oxidoreductases / biosynthesis*
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Aldehyde Oxidoreductases / genetics
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Aldehyde Oxidoreductases / physiology
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Animal Feed
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Animals
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Dendritic Cells / enzymology
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Dendritic Cells / immunology
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Dendritic Cells / pathology
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Gene Expression Regulation / immunology*
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Intestinal Mucosa / enzymology*
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Intestinal Mucosa / immunology
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Intestinal Mucosa / pathology
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Intestine, Small / enzymology*
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Intestine, Small / immunology
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Intestine, Small / pathology
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Lymph Nodes / enzymology*
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Lymph Nodes / immunology
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Lymph Nodes / pathology
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Mesentery / enzymology
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Mesentery / immunology
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Mesentery / pathology
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Mice
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Retinal Dehydrogenase / biosynthesis*
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Retinal Dehydrogenase / genetics
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Retinal Dehydrogenase / physiology
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Stromal Cells / enzymology
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Stromal Cells / immunology
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Stromal Cells / pathology
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Tretinoin / physiology*
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Vitamin A / administration & dosage
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Vitamin A / physiology*
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Vitamin A Deficiency / enzymology
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Vitamin A Deficiency / immunology
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Vitamin A Deficiency / pathology
Substances
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Vitamin A
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Tretinoin
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Aldehyde Oxidoreductases
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RALDH2 protein, mouse
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Retinal Dehydrogenase