Activation of the aryl hydrocarbon receptor suppresses sensitization in a mouse peanut allergy model.

Food allergy is an increasing health problem in Western countries. Previously, it has been shown that the intensity of food allergic reactions can be regulated by regulatory T (T(reg)) cells. In addition, it has been shown that activation of the aryl hydrocarbon receptor (AhR) regulates T-cell responses by induction of T(reg) cells. Therefore, we hypothesized that activation of the AhR pathway can suppress development of food allergic responses through the induction of T(reg) cells. This was investigated by using a mouse model for peanut allergy. C3H/HeOuJ mice (AhR(b)(-2)) were sensitized to peanut by administering peanut extract (PE) by gavage in the presence of cholera toxin and were treated with the prototypical AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (0.6, 1.7, 5, and 15 μg/kg body weight) on days 3 and 11 orally. The functional role of CD4(+)CD25(+)Foxp3(+) T(reg) cells was investigated by depleting these cells with anti-CD25 mAb during sensitization to PE. TCDD treatment dose dependently suppressed sensitization to peanut (PE-specific IgE, IgG1, and IgG2a and PE-induced IL-5, IL-10, and IL-13, respectively). The percentage, but not the number, of CD4(+)CD25(+)Foxp3(+) T(reg) cells dose dependently increased by AhR activation in both spleen and mesenteric lymph nodes. Depletion of CD4(+)CD25(+)Foxp3(+) T(reg) cells markedly reversed the suppressive effect of TCDD on PE-specific antibody levels and PE-induced IL-5, IL-10, and IL-13 cytokine production. Present data demonstrate for the first time that activation of the AhR by TCDD suppressed the development of Th2-mediated food allergic responses. A functional shift within the CD4(+) cell population toward CD4(+)CD25(+)Foxp3(+) T(reg) cells appeared to underlie this effect. This suggests that the AhR pathway might provide potential therapeutic targets to treat food allergic diseases.