Epithelial cell IKKβ regulates eosinophil levels in the intestine and severity of allergic responses to ingested allergens

Abstract

Abstract Allergic sensitization to food allergens has subsequent potential to developing allergic responses in the gastrointestinal tract, but also to skin or lung. Our previous study showed that lack of IKKβ in intestinal epithelial cells regulates favors IgA responses to ingested allergen, which in turn limits the severity of allergic responses in the airway. In this study we investigated whether intestinal epithelial IKKβ also regulated allergic responses to oral antigens. Wild-type C57BL/6 and IKKβΔIEC mice, which lack IKKβ in intestinal epithelial cells, were orally sensitized to a food antigen in the presence of cholera toxin. Allergen-specific serum IgE responses and fecal IgA responses were similar between the groups. However, after oral allergen-challenge, IKKβΔIEC mice only developed minimal clinical and histological signs of allergy, including drop in body temperature and mucus in small intestinal villi and crypts. Interestingly, IKKβΔIEC mice expressed lower levels of CCL11 (eotaxin) and eosinophils than control wild-type mice and their levels were only weakly increased after oral allergen sensitization and challenge. In summary, this study reveals a new role of intestinal epithelial cells in the regulation of allergy in the GI tract through a NF-κB-CCL11 axis.