Retinoic acid imprints gut-homing specificity on T cells.
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.
Iwata
Makoto
M
Mitsubishi Kagaku Institute of Life Sciences, 11 Minamiooya, Machida-shi, Tokyo 194-8511, Japan. iwata@libra.ls.m-kagaku.co.jp
Hirakiyama
Asami
A
Eshima
Yuko
Y
Kagechika
Hiroyuki
H
Kato
Chieko
C
Song
Si-Young
SY
D000818:Animals; D000970:Antineoplastic Agents / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007150:Immunohistochemistry; D016023:Integrins / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007422:Intestines / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D054388:Receptors, CCR; D019707:Receptors, Chemokine / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016201:Receptors, Lymphocyte Homing / Q000276:immunology / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D014212:Tretinoin / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D018523:Tropism / Q000276:immunology*
D000970:Antineoplastic Agents; C119309:CC chemokine receptor 9; D004791:Enzyme Inhibitors; D016023:Integrins; D054388:Receptors, CCR; D019707:Receptors, Chemokine; D016201:Receptors, Lymphocyte Homing; D018168:Receptors, Retinoic Acid; C071777:integrin alpha4beta7; D014212:Tretinoin