Yining Jin Allison P. Boss Jenna K. Bursley Caitlin Wilson VENUGOPAL GANGUR Cheryl E. Rockwell ^*

• Michigan State University, East Lansing, United States

Immune-mediated adverse reactions to food allergens are rising at a striking rate, for reasons that are not completely understood. Our previous studies suggest that the stress-activated transcription factor Nrf2 (Nuclear factor erythroid 2 -related factor) promotes Th2 differentiation, while inhibiting Th1 differentiation. In the present studies, we investigated the effect of Nrf2 activation on sensitization and anaphylaxis in response to food allergen in BALB/c mice. Our results demonstrate that the common food preservative tBHQ (tertbutylhydroquinone) strongly increases IgE sensitization to ovalbumin (OVA) with a concurrent increase in plasma IgG1 concentrations. In addition, tBHQ in diet also exacerbated anaphylaxis and increased mast cell degranulation. In a recall response, tBHQ promoted a type 2 T cell response. Notably, adoptive transfer studies in SCID recipient mice indicate that Nrf2 expression in CD4 + T cells is critical to sensitization and anaphylaxis in response to food allergen. Likewise, the effects of tBHQ on sensitization and challenge are dependent on Nrf2 expression in CD4 + T cells. Overall, these studies point to a key role for Nrf2 in the immune response to food allergen.• The synthetic food additive, tBHQ, promotes IgE sensitization in response to OVA.• Anaphylaxis following oral challenge was exacerbated in mice on a tBHQ diet.• The effects of tBHQ are dependent on expression of Nrf2 in CD4 T cells.