Oral Immunotherapy with a Phosphorylated Hypoallergenic Allergen Ameliorates Allergic Responses More Effectively Than Intact Allergen in a Murine Model of Buckwheat Allergy

SCOPE: Buckwheat is a common food allergen frequently consumed in Asian countries, with Fag e 1 and Fag e 2 being the major buckwheat allergens. The purpose of this study is to prepare an oral immunotherapy agent by attenuating these allergens via phosphorylation. The immunomodulatory effects of phosphorylated Fag e 2 (P-Fag e 2) in a mouse model of buckwheat allergy are evaluated. METHODS AND RESULTS: Phosphorylated Fag e 1 (P-Fag e 1) and P-Fag e 2 are prepared by dry-heating in the presence of pyrophosphate. Subsequent dot-blot analysis using serum from food-allergic patient indicates that both proteins exhibit reduced allergenicity upon phosphorylation. Mice subjected to oral administration of P-Fag e 2 for 6 weeks exhibit decreased specific serum IgE and increased specific IgA after Fag e 2 sensitization compared to the sham-treated mice. Moreover, the Peyer's patches (PP) of phosphorylated antigen-fed mice show decreased IL-4 production and induction of T follicular helper (Tfh) cells. Increased production of IL-6 is observed in the CD11c+ cells isolated from the PPs of P-Fag e 2-fed mice. CONCLUSION: These results indicate that attenuated allergens can suppress Th2-induced allergic responses via induction of Tfh cells, which are regulated by IL-6 secreted from dendritic cells.