Functions of an Environmental Allergen in Induction of Food Allergy.

Abstract

Abstract Food allergy can be induced in neonatal mice with heterozygous skin barrier mutations and skin co-exposure to detergent, food allergen and a ubiquitous environmental allergen Alternaria Alternata (Alt) at doses in dust. In this study it was determined whether cytokines are induced by Alt in development of allergy to peanut extract (PNE). In preliminary RNAseq data, Alt induced expression of IL33, oncostatin M (OSM) and amphiregulin (Areg) in the skin of neonatal flakey tail (FT+/−) mice with heterozygous skin barrier mutations. In FT+/−, but not WT neonates, qPCR analyses revealed skin expression of IL33 and OSM following Alt or Alt+PNE exposure compared to neonates with saline skin exposure, while IL33 and OSM were not induced by skin exposure to PNE alone. The expression of Areg was induced by Alt, PNE or Alt+PNE in FT+/− neonates. It was determined whether intradermal injection of recombinant IL33 (rIL33), rAreg or rOSM could substitute for Alt during skin sensitization to PNE. PNE skin sensitization with intradermal rIL33 was sufficient for oral PNE induced anaphylaxis, whereas skin sensitization with intradermal rAreg or rOSM during skin exposure to PNE was not. Injection of neutralizing antibodies for Areg and OSM blocked anaphylaxis in Alt+PNE exposed neonates, indicating that Areg and OSM are required for PNE-induced anaphylaxis prior to skin sensitization. Analysis of skin IL33, Areg and OSM gene expression and plasma protein for IL33, Areg and OSM defined a pathway for IL33, Areg and OSM in Alt+PNE skin. Thus, Alt stimulated expression of IL33 and a pathway of OSM and Areg in concert with PNE to induce food allergy in FT+/− pups. These data have important implications for studies of detection of risks for sensitization to food allergens.