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Mucosal Immunol. 2018 Mar;11(2):394-403. doi: 10.1038/mi.2017.61. Epub 2017 Jun 28.

IL-33 promotes gastrointestinal allergy in a TSLP-independent manner.

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Immunology Program, Benaroya Research Institute, Seattle, Washington, USA.
Division of Allergy and Infectious Diseases, University of Washington School of Medicine, Seattle, Washington, USA.
Division of Allergy-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Department of Inflammation Research, Amgen Inc., Seattle, Washington, USA.
Department of Immunology, University of Washington School of Medicine, Seattle, Washington, USA.


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. Thymic stromal lymphopoietin (TSLP) and interleukin (IL)-33 are two cytokines that may drive type 2 responses in the skin; both are potential targets in the treatment of allergic diseases. We tested the functional role of IL-33 and the interplay between IL-33 and TSLP in mouse models of atopic march and gastrointestinal (GI) allergy. IL-33-driven allergic disease occurred in a TSLP-independent manner. In contrast, mice lacking IL-33 signaling were protected from onset of allergic diarrhea in TSLP-driven disease. Epithelial-derived IL-33 was important in this model, as specific loss of IL-33 expression in the epithelium attenuated cutaneous inflammation. Notably, the development of diarrhea following sensitization with TLSP plus antigen was ameliorated even when IL-33 was blocked after sensitization. Thus, IL-33 has an important role during early cutaneous inflammation and during challenge. These data reveal critical roles for IL-33 in the "atopic march" that leads from AD to GI allergy.

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