Induction of Oral Tolerance by Pepsin-Digested Gliadin Retaining T Cell Reactivity in a Mouse Model of Wheat Allergy.

Abstract:

BACKGROUND:Wheat is known as the most widely consumed food all over the world. Although many types of wheat allergy have been recognized, their treatment still has a long way to go due to the complex pathogenesis. Oral immunotherapy (OIT) is under investigation for the treatment of wheat allergies. Previous studies have demonstrated that OIT using intact wheat allergens can induce tolerance, but is accompanied by a high risk of anaphylactic reactions. OBJECTIVES:Our objective was to prepare modified wheat allergens with hypoallergenic and tolerance-inducing properties to reduce adverse effects during immunotherapy. METHODS:Wheat gliadin was degraded by hydrolysis with pepsin and trypsin, and then the hydrolysate was deamidated with hydrochloric acid. The IgE-binding capacity and T cell reactivity of the degraded gliadins were evaluated in vitro. Pepsin-digested gliadin (peptic-GLI) was applied in a mouse model to investigate whether it would induce oral tolerance. RESULTS:Degradation with pepsin decreased IgE-binding capacity and maintained T cell reactivity. Oral administration of peptic-GLI to mice before sensitization and challenge with gliadin could significantly suppress the production of IgE, IgG1, and type 2 T helper cytokines. Moreover, the development of anaphylactic reactions and allergic responses of the small intestine induced by gliadin challenge were inhibited by oral administration of peptic-GLI. CONCLUSIONS:The findings of this study indicate that peptic-GLI with low allergenicity and potential for tolerance induction may become useful in wheat immunotherapy with less adverse effects.

authors

Li X,Miyakawa T,Takano T,Nakajima-Adachi H,Tanokura M,Hachimura S

doi

10.1159/000506945

subject

Has Abstract

pub_date

2020-01-01 00:00:00

pages

446-455

issue

6

eissn

1018-2438

issn

1423-0097

pii

000506945

journal_volume

181

pub_type

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