Abstract
For a preferential homing of T cells to the gut, expression of the integrin alpha4beta7 and the chemokine receptor CCR9 is essential and is induced by antigenic stimulation with dendritic cells from the gut-associated lymphoid organs. Here, we show that the vitamin A (retinol) metabolite, retinoic acid, enhances the expression of alpha4beta7 and CCR9 on T cells upon activation and imprints them with the gut tropism. Dendritic cells from the gut-associated lymphoid organs produced retinoic acid from retinol. The enhanced alpha4beta7 expression on T cells by antigenic stimulation with these dendritic cells was suppressed by the retinal dehydrogenase inhibitor citral and the retinoic acid receptor antagonist LE135. Accordingly, vitamin A deficiency caused a reduction in alpha4beta7(+) memory/activated T cells in lymphoid organs and a depletion of T cells from the intestinal lamina propria. These findings revealed a novel role for retinoic acid in the imprinting of gut-homing specificity on T cells.
MeSH terms
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Animals
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Antineoplastic Agents / immunology
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Antineoplastic Agents / metabolism
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Antineoplastic Agents / pharmacology*
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Dendritic Cells / immunology
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Dendritic Cells / metabolism
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Enzyme Inhibitors / pharmacology
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Immunohistochemistry
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Integrins / drug effects
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Integrins / immunology
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Integrins / metabolism
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Intestinal Mucosa / cytology
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Intestinal Mucosa / immunology
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Intestinal Mucosa / metabolism
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Intestines / cytology
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Intestines / immunology*
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Lymphocyte Activation / drug effects
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Lymphocyte Activation / physiology
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Lymphoid Tissue / cytology
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Lymphoid Tissue / immunology
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Lymphoid Tissue / metabolism
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Mice
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Mice, Transgenic
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Receptors, CCR
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Receptors, Chemokine / drug effects
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Receptors, Chemokine / immunology
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Receptors, Chemokine / metabolism
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Receptors, Lymphocyte Homing / immunology
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Receptors, Lymphocyte Homing / metabolism
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Receptors, Retinoic Acid / drug effects
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Receptors, Retinoic Acid / immunology
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Receptors, Retinoic Acid / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism
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Tretinoin / immunology
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Tretinoin / metabolism
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Tretinoin / pharmacology*
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Tropism / immunology*
Substances
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Antineoplastic Agents
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CC chemokine receptor 9
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Enzyme Inhibitors
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Integrins
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Receptors, CCR
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Receptors, Chemokine
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Receptors, Lymphocyte Homing
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Receptors, Retinoic Acid
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integrin alpha4beta7
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Tretinoin