Intestinal epithelial cells IKKβ regulate allergic responses in the skin (P6053)

Abstract

Abstract The sites where immune responses are initiated are believed to play a key role at shaping subsequent responses at distant mucosal sites. We have previously shown that IKKβ in intestinal epithelial cells (IECs) shapes the immune responses to ingested antigens and influences airway responses to subsequent antigen exposure via regulation of IgA and Th17. People with food allergy often suffer from allergic airway and/or skin diseases like asthma or atopic dermatitis but it is unknown whether T cells sensitized in the gut promote inflammation at different mucosal surfaces through the same mechanism. Using a model of oral antigen sensitization and mice with cell-specific deletion of IKKβ, we addressed the contribution of IECs to regulatory crosstalk between the gut and skin. Control C57BL/6 mice and mice deficient in IKKβ in IEC (IKKβΔIEC) were orally sensitized by administration of ovalbumin and cholera toxin as adjuvant. All groups developed similar levels of antigen-specific IgE and IgG1 responses, but IgG2b responses were enhanced in IKKβΔIEC. Subsequent epicutaneous challenges of control mice with ovalbumin induced skin inflammation characterized by increased epidermal thickness and dermal infiltration of eosinophils. Interestingly, both the epidermal thickness and dermal infiltration of eosinophils were reduced in IKKβΔIEC. Ongoing studies will determine mechanisms underlying the protective effect of IKKβ in intestinal epithelial cells against allergic responses in the skin.