Distinct tissue-specific functions for TSLP and IL-33 in the atopic march

Abstract Atopic dermatitis (AD) often precedes asthma and food allergy, indicating that epicutaneous sensitization to allergens may be important in the induction of allergic responses at other barrier surfaces. Our study demonstrated a central role for IL-33 in this “atopic march.” We showed that mice exposed to antigen in the skin, in the presence of IL-33, developed severe airway inflammation when later challenged in the lung, and developed allergic diarrhea following oral antigen challenge. In addition, IL-33-driven allergic disease occurred in a thymic stromal lymphopoietin (TSLP)-independent manner. In contrast, IL-33 signaling was required for local inflammation following epicutaneous TSLP/OVA sensitization and during challenge in allergic gastrointestinal disease, but was dispensable during challenge in TSLP-mediated airway disease. These data reveal critical, site-specific roles for IL-33 in the “atopic march” that lead from atopic dermatitis to allergic asthma and gastrointestinal allergy.