Augmentation of Retinoic Acid Production in the Colonic Epithelial Cells Ameliorates Food Allergy via the Induction of Foxp3+ Regulatory T Cells in a Murine Model

Background & Aim: Regulatory T cells (Tregs) in the lamina propria play a critical role in maintaining peripheral tolerance in the gut, and retinoic acid (RA) is required for induction of Tregs. Although colonic epithelial cells (CECs) produce RA, it remains unclear whether the RA production in the CECs leads to the induction of Tregs. It is reported that puerarin, isoflavone derivatives, exerts anti-inflammatory effects in several epithelial cells. Thus, we investigated the effect of puerarin in a food allergy (FA) mouse model.

Methods: BALB/c mice were systemically sensitized and then orally challenged with ovalbumin in the FA mouse model.

Results: Puerarin treatment ameliorated FA. The level of ALDH1A1 mRNA, RA generating enzyme, in the CECs and the proportion of Foxp3⁺CD4⁺ cells were significantly higher in the puerarin-treated FA mouse colon. The induction of Foxp3⁺CD4⁺cells by puerarin was reduced by pretreatment of LE540, retinoic acid receptor antagonist. In addition, the therapeutic effect of puerarin was suppressed by pretreatment of LE540 in the FA model.

Conclusion: The present findings suggest that the augmentation of RA production in the CECs enhances the induction of Tregs and ameliorates FA in the mouse model.