Expression of retinoic acid receptors in intestinal mucosa and the effect of vitamin A on mucosal immunity

Objective: To explore the mechanism of vitamin A (VA) modulation of mucosal immunity, the expression of retinoic acid receptors in intestinal mucosa was measured, and the effect of VA on intestinal dendritic cells (DCs) and mucosal cytokine production was examined. Methods: The expression of retinoic acid receptor (RAR-alpha, RAR-beta, RAR-gamma, RXR-alpha, RXR-beta, RXR-gamma) mRNA, the distribution and number of DCs, and the protein secretion of interleukin (IL)-12, T-helper type 1/2 cells (interferon [IFN]-gamma/IL-4), and regulatory (IL-10) cytokines in the mucosa of terminal ileum in normal rats and rats with VA deficiency (VAD) were detected by reverse transcriptase polymerase chain reaction, immunohistochemistry, and enzyme-linked immunosorbent assay, respectively. The effect of all-trans retinoic acid on the number and maturation of DCs and the gene expression of RAR-alpha and cytokines listed earlier in cultured Peyer's patches were examined by flow cytometry and reverse transcriptase polymerase chain reaction, respectively. Results: In the intestinal mucosa of VAD rats, RAR-alpha mRNA was downregulated, DC number increased, the protein secretion of IL-12 was increased, but the secretion of IFN-gamma and IL-10 decreased. In in vitro cultured Peyer's patches, all-trans retinoic acid promoted DC maturation, upregulated RAR-alpha mRNA, reduced IL-12 and IFN-gamma, but increased IL-10 gene expression; these effects of all-trans retinoic acid were reversed when cultured with Ro 41-5253 (a specific antagonist of RAR-alpha). Conclusion: Vitamin A may be potent in reducing intestinal inflammation and restoring impaired antibody responses in a VAD situation. The effect of VA on DCs could be an important mechanism contributing to altered mucosal immunity. RAR-alpha may mostly play a role in the action of VA. (C) 2010 Elsevier Inc. All rights reserved.