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

Abstract

Buckwheat is a common food allergen frequently consumed in Asian countries, with Fage1 and Fage2 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 Fage2 (P-Fage2) in a mouse model of buckwheat allergy are evaluated. Phosphorylated Fage1 (P-Fage1) and P-Fage2 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-Fage2 for 6 weeks exhibit decreased specific serum IgE and increased specific IgA after Fage2 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-Fage2-fed mice. 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.