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

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Induction of Oral Tolerance by Pepsin-Digested Gliadin Retaining T Cell Reactivity in a Mouse Model of Wheat Allergy (1)

oral administration of intact allergens can cause adverse effects and even lead to a severe allergic reaction. Anaphylaxis could be induced during the escalation phase of wheat OIT. Thus, modified allergens characterized by hypoallergenicity and potential for tolerance induction have become desirable for the treatment of wheat allergy. Enzymatic hydrolysis combined with acid deamidation has been shown to increase the solubility, foaming, and emulsifying properties of gluten.

Sensitized mice had a notable increase in the IgE-binding capacity of both gliadin and degraded gliadins (peptic-GLI, PT-GLI, and HCl-PT-GLI) compared to unsensitized mice. The IgE-binding capacity of peptic-GLI, PT-GLI, and HCl-PT-GLI showed a significant decrease compared to that of gliadin in the sera of sensitized mice.

The rectal temperature of the control group significantly decreased after challenge with gliadin for 15 min.

The level of proliferation of CD4+ T cells was significantly higher in the gliadin group than in the control group regardless of the activation conditions. The gliadin group showed significantly higher proliferation of CD4+ T cells in response to activation with gliadin or peptic-GLI compared to activation with PT-GLI or HCl-PT-GLI.

The upregulation of gliadin-specific IgE and IgG1 caused by immunization with gliadin (control group) was suppressed when gliadin or peptic-GLI was orally administered before gliadin sensitization (light gray bars). Similar results were observed after the challenge.

Spleen and MLN CD4+ T cells from mice in the control group secreted substantial levels of IL-4 and IL-5 in response to gliadin (0.5 mg/mL) stimulation. However, the secretion of IL-4 and IL-5 was significantly suppressed by oral administration of gliadin or peptic-GLI before gliadin sensitization.

The histamine production in the control group was significantly higher than that in the other two groups, whereas no significant difference was observed between the gliadin and peptic-GLI groups.

mMCP-1 has been used as a mast cell activation marker in food-induced anaphylaxis. The measurement of histamine level and mMCP-1 expression was to reflect the situation of mast cell degranulation in the small intestine. The expansion of intestinal mast cells elicited by mechanical skin injury promotes oral anaphylaxis.

1. X. Li, T. Miyakawa, T. Takano, H. Nakajima-Adachi, M. Tanokura, S. Hachimura, Induction of Oral Tolerance by Pepsin-Digested Gliadin Retaining T Cell Reactivity in a Mouse Model of Wheat Allergy. Int. Arch. Allergy Immunol. 181, 446–455 (2020).

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