BACKGROUND: Although peanut and soybean proteins share extensive amino acid sequence homology, the incidence and severity of allergic reactions to soy are much less than those to peanut. Soybeans are rich in anti-inflammatory isoflavones and are the most common source of isoflavones in the human food supply. OBJECTIVE: We hypothesized that the active isoflavones in the gut milieu are capable of modulating immune responses to dietary antigens by regulating dendritic cell (DC) function. METHODS: We tested this hypothesis in a murine model of peanut allergy and in human monocyte-derived dendritic cells (MDDCs). C3H/HeJ mice were fed a diet containing genistein and daidzein. The mice were sensitized and challenged with peanut, and the anaphylactic symptoms were compared with those of mice fed a soy-free diet. Human MDDCs were activated with cholera toxin in the presence of isoflavones. The surface expression of DC activation markers and DC-mediated effector functions were analyzed by means of flow cytometry. RESULTS: Dietary isoflavones significantly reduced the anaphylactic symptoms and mast cell degranulation in vivo after peanut challenge. Serum peanut-specific antibodies were markedly reduced in mice fed the isoflavone diet. Isoflavones inhibited cholera toxin-induced DC maturation in the mesenteric lymph nodes and human MDDCs and subsequent DC-mediated CD4(+) T-cell function in vitro. CONCLUSIONS: These data suggest that dietary isoflavones suppress allergic sensitization and protect against peanut allergy in vivo. Dietary supplementation of soybean isoflavones could be a novel strategy to prevent the development of allergic reactions to food.
BACKGROUND: Although peanut and soybean proteins share extensive amino acid sequence homology, the incidence and severity of allergic reactions to soy are much less than those to peanut. Soybeans are rich in anti-inflammatory isoflavones and are the most common source of isoflavones in the human food supply. OBJECTIVE: We hypothesized that the active isoflavones in the gut milieu are capable of modulating immune responses to dietary antigens by regulating dendritic cell (DC) function. METHODS: We tested this hypothesis in a murine model of peanutallergy and in human monocyte-derived dendritic cells (MDDCs). C3H/HeJ mice were fed a diet containing genistein and daidzein. The mice were sensitized and challenged with peanut, and the anaphylactic symptoms were compared with those of mice fed a soy-free diet. Human MDDCs were activated with cholera toxin in the presence of isoflavones. The surface expression of DC activation markers and DC-mediated effector functions were analyzed by means of flow cytometry. RESULTS: Dietary isoflavones significantly reduced the anaphylactic symptoms and mast cell degranulation in vivo after peanut challenge. Serum peanut-specific antibodies were markedly reduced in mice fed the isoflavone diet. Isoflavones inhibited cholera toxin-induced DC maturation in the mesenteric lymph nodes and human MDDCs and subsequent DC-mediated CD4(+) T-cell function in vitro. CONCLUSIONS: These data suggest that dietary isoflavones suppress allergic sensitization and protect against peanutallergy in vivo. Dietary supplementation of soybeanisoflavones could be a novel strategy to prevent the development of allergic reactions to food.