Dietary Resveratrol Prevents the Development of Food Allergy in Mice

Masashi Hisamoto,Shuji Matsuoka,Yui Okada,Ko Okumura,Yuki Nakamura,Hideoki Ogawa,Kayoko Ishimaru,Atsuhito Nakao,Stefan Bereswill,Kyoko Oh-Oka,Tohru Okuda

doi:10.1371/journal.pone.0044338

Abstract

BackgroundResveratrol is a bioactive polyphenol enriched in red wine that exhibits many beneficial health effects via multiple mechanisms. However, it is unclear whether resveratrol is beneficial for the prevention of food allergy. This study investigated whether resveratrol inhibited the development of food allergy by using a mouse model of the disease.Methodology/Principal FindingsMice fed standard diet or standard diet plus resveratrol were sensitized by intragastric administration of ovalbumin (OVA) and mucosal adjuvant cholera toxin (CT). Several manifestations of food allergy were then compared between the mice. The effects of resveratrol on T cells or dendritic cells were also examined by using splenocytes from OVA-specific T cell-receptor (TCR) transgenic DO11.10 mice or mouse bone marrow-derived dendritic cells (BMDCs) in vitro. We found that mice fed resveratrol showed reduced OVA-specific serum IgE production, anaphylactic reaction, and OVA-induced IL-13 and IFN-ã production from the mesenteric lymph nodes (MLNs) and spleens in comparison to the control mice, following oral sensitization with OVA plus CT. In addition, resveratrol inhibited OVA plus CT-induced IL-4, IL-13, and IFN-ã production in splenocytes from DO11.10 mice associated with inhibition of GATA-3 and T-bet expression. Furthermore, resveratrol suppressed the OVA plus CT-induced CD25 expression and IL-2 production in DO11.10 mice-splenocytes in association with decreases in CD80 and CD86 expression levels. Finally, resveratrol suppressed CT-induced cAMP elevation in association with decreases in CD80 and CD86 expression levels in BMDCs.Conclusions/SignificanceIngestion of resveratrol prevented the development of a food allergy model in mice. Given the in vitro findings, resveratrol might do so by inhibiting DC maturation and subsequent early T cell activation and differentiation via downregulation of CT-induced cAMP activation in mice. These results suggest that resveratrol may have potential for prophylaxis against food allergy.

Highlights

Food allergy is defined as an immune-mediated pathological reaction toward food antigens, which is a major health concern and epidemic in developed countries [1,2,3]
OVA-specific IL-13 and IFN-aproductions from splenocytes and mesenteric lymph nodes (MLN)-derived cells were decreased in resveratrol-fed mice in comparison to those in control mice, following sensitization with OVA plus cholera toxin (CT) (Figure 1D)
The frequencies of apoptotic cells in splenocytes and MLN cells freshly isolated from the mice fed standard diet and the mice fed the standard diet plus resveratrol were comparable based on propidium iodide (PI) and Annexin V staining (Figure S1 A and B)

Summary

Introduction

Food allergy is defined as an immune-mediated pathological reaction toward food antigens, which is a major health concern and epidemic in developed countries [1,2,3]. The development of new approaches to prevent the disease is of significant importance for public health because allergen avoidance is currently the only way available for prevention of food allergy [7]. In spite of these extensive studies on the roles of resveratrol in human health and diseases, it remains unclear whether resveratrol is beneficial for food allergy. Resveratrol is a bioactive polyphenol enriched in red wine that exhibits many beneficial health effects via multiple mechanisms. It is unclear whether resveratrol is beneficial for the prevention of food allergy. This study investigated whether resveratrol inhibited the development of food allergy by using a mouse model of the disease

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