The role of the stress-activated transcription factor Nrf2 in OVA-induced food allergy

Abstract

Abstract Food allergies are rising at a striking rate, but the underlying cause is unclear. The purpose of the studies was to determine the effect of the food preservative tert-butylhydroquinone (tBHQ) in a mouse model of food allergy. Our preliminary studies show that skin-sensitization with OVA induced an elevated OVA-IgE level in mice on a tBHQ diet. Likewise, in response to oral challenge, a greater decrease in body temperature during anaphylaxis was observed in the tBHQ group. Previously published in vitro studies suggest that tBHQ promotes Th2 polarization through activation of the stress-activated transcription factor, Nrf2. Therefore, we proposed the hypothesis that tBHQ exacerbates allergic response in OVA sensitized mice through activation of Nrf2. We implemented adoptive transfers of CD4 T cells from wild-type or Nrf2-null mice into immunodeficient mice (all mice received wild-type B cells). The study revealed marked genotype differences. Notably, dietary tBHQ had little effect on food allergy in recipients of Nrf2-deficient CD4 T cells. These mice showed attenuated sensitization as compared to wild-type CD4 T cells recipients. Strikingly, mice receiving Nrf2-deficient T cells did not become anaphylactic following challenge. In contrast, tBHQ caused an increase in OVA-IgE levels and a greater drop in body temperature in mice receiving wild-type CD4 T cells, suggesting these effects are Nrf2 dependent. In addition, recipients of Nrf2-deficient CD4 T cells showed an attenuated percentage of Th2 cells and mast cell degranulation response, following challenge. Taken together, these data suggest a critical role for Nrf2 during food allergy and demonstrate that tBHQ exacerbates food allergy in a CD4 T cell-Nrf2 dependent manner.