Retinoic Acid Imprints Gut-Homing Specificity on T Cells

Mitsubishi Kagaku Institute of Life Sciences, 11 Minamiooya, Machida-shi, Tokyo 194-8511, Japan.
Immunity (Impact Factor: 19.75). 11/2004; 21(4):527-38. DOI: 10.1016/j.immuni.2004.08.011
Source: PubMed

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.

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    • "Retinoic acid has been shown to inhibit Th17 and the conversion of Tregs into T follicular helper cells, and induce intestinal mucosal homing molecules CCR9 and a 4 b 7 (Benson et al. 2007; Iwata et al. 2004; Mora et al. 2003; Mucida et al. 2007; Sun et al. 2007; Takahashi et al. 2012). Also, retinoic acid is important for IgA-secreting cells, since mice deficient for vitamin A lack these cells in the small intestine (Mora et al. 2006). "
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    • "In our work we found that RALDH2 can be the responsible for RA synthesis in dLNs. It has been shown that RALDH2 is essential for embryonic development (Duester, 2001), and in immune cells, RALDH2 has been attributed to DCs from mesenteric lymph nodes and also stromal cells (Iwata et al., 2004; Molenaar et al., 2009). These data indicate that in dLNs there are not only RA-sensing cells, such as T cells, but also RA synthesis takes place in the graft dLNs during the allo-response and appears to be essential for T cell function. "
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    • "Retinoic acid has been shown to mediate mucosal IgA production [14] and intestinal homing of IgA + plasma cell [15] and T-cells [16]. In addition to mediating these responses, vitamin A is also essential for normal T-cell responses in the gut mucosa [16]. VAD alters cytokine responses such as polarization toward increased T-helper cell type- 1(Th1) cytokine responses in infants [17] and mice [18]. "
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