Induction of Peanut Allergy in Neonatal Mice by Alternaria Alternata through Skin

Oral peanut-induced anaphylaxis is induced in neonatal FT+/- mice with skin barrier genes mutations and co-exposure to the allergen Alternaria alternata (Alt), peanut extract (PNE) and detergent. However, the function of Alt in initiation of food allergy is not known. To address this, our bulk RNAseq, scRNAseq and RT-qPCR analyses demonstrated that Alt induced expression of Il33, Osm and Areg in the skin of FT+/- but not wild type (WT) neonates. In skin of FT+/- neonates, Il33 and Osm expression was induced by Alt or Alt&PNE but not by PNE alone. Areg in FT+/- skin was induced by Alt, PNE or Alt&PNE. Areg and OSM were required for oral PNE-induced anaphylaxis since anaphylaxis was inhibited by anti-Areg or anti-OSM neutralizing antibodies during Alt&PNE skin sensitization. Furthermore, 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 sufficient for anaphylaxis to oral PNE challenge. These data defined a IL33 pathway and an Areg/OSM pathway in Alt&PNE FT+/- skin for IgE, MCPT1 and anaphylaxis. The data in this report have important implications for studies of detection of risks for sensitization to food allergens.