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The role of the stress‐activated transcription factor Nrf2 in OVA‐induced food allergy
Author(s) -
Jin Yining,
Boss Allison,
Bursley Jenna,
Gangur Venugopal,
Rockwell Cheryl
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.05357
Subject(s) - transcription factor , food allergy , allergy , microbiology and biotechnology , chemistry , immunology , biology , genetics , gene
Immune‐mediated adverse reactions to food allergens are rising at a striking rate, but the underlying cause is unknown. The purpose of the present studies was to determine the effect of the food preservative tert ‐butylhydroquinone (tBHQ) on anaphylaxis in a mouse model of food allergy. Our preliminary studies demonstrate that skin‐sensitization with OVA induced a markedly higher OVA‐specific IgE response in mice on a tBHQ diet. Likewise, in response to OVA challenge by the oral route, a greater decrease in body temperature during anaphylaxis was observed in the tBHQ‐treated group. Previously published in vitro studies suggest that tBHQ promotes Th2 polarization, a key step in the development of allergy, through activation of the stress‐activated transcription factor, Nrf2. Therefore, we proposed the hypothesis that tBHQ exacerbates allergic response in ovalbumin (OVA) sensitized mice through activation of Nrf2. We implemented adoptive transfers of CD4 T cells from wild‐type or Nrf2‐null mice into immunodeficient SCID mice (all mice also 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 markedly attenuated sensitization as compared to mice who received wild‐type CD4 T cells. Strikingly, mice receiving Nrf2‐deficient T cells did not become anaphylactic following OVA challenge. In contrast, tBHQ caused an increase in OVA‐IgE plasma 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 a greatly attenuated percentage of Th2 cells and mucosal mast cell degranulation response, following OVA challenge. Taken together, these data suggest a critical role for Nrf2 during food allergen‐induced sensitization and anaphylaxis and demonstrate that tBHQ exacerbates food allergy in a CD4 T cell‐ Nrf2 dependent manner in mice.