The Aryl Hydrocarbon Receptor and Food Allergy

Abstract

Currently, food allergy is a major health problem with an estimated prevalence of about 5% in young children and 3-4% in adults and the prevalence is increasing. However, no cure or approved treatment is available, despite the increased knowledge of mechanisms playing a role in food allergy. The aryl hydrocarbon receptor (AhR) mediates toxic responses to a variety of pollutants, including dioxins. Interestingly, activation of the aryl hydrocarbon receptor (AhR) by dioxins has also been shown to suppress a variety of immune responses by affecting various cells of the immune system, including dendritic cells, regulatory T cells and the Th1/Th2 cell balance. Interestingly, these cells play a major role in food allergy, because they are involved in the induction of either tolerance of allergic sensitization. The aim of this thesis was to address whether and how AhR activation suppresses allergic sensitization by using a mouse model for peanut allergy. In addition, it was studied whether AhR activation could be used as a therapy or could improve immunotherapy for food allergy. Immunotherapy is not successfully applied yet for food allergy, because of the unacceptable high risk for side effects. The data described in this thesis show that AhR activation by dioxin-like compounds suppresses allergic sensitization by reducing the absolute number of precursor and effector T cells, by preserving regulatory T cells and by suppressing the interaction of dendritic cells with T helper 1 and T helper 2 cells. Furthermore, data in this thesis show that activation of the AhR affects immunotherapy for food allergy. The results in this thesis have contributed to knowledge about the role of the AhR in the immune system, especially in the context of food allergic responses. Future research should elucidate whether and how AhR activation can be used to interfere in food allergic responses in humans. This may lead to new prevention strategies and therapeutic possibilities for food allergy.