The impact of different challenge protocols on immune response in epicutaneously sensitized mice with food allergy†

Abstract

The skin serves as a critical non-digestive route for the entry of food allergens into the body. Food allergens can penetrate through the disrupted skin barrier, resulting in immune sensitization, and subsequently triggering allergic reactions upon oral re-exposure to the same allergen. In this study, an epicutaneous sensitization animal model was established to characterize its features of food allergy (FA) and to investigate the impact of different challenge protocols on immune response in sensitized mice. The results demonstrated that epicutaneously sensitized mice exhibited various FA symptoms, including skin scratching, diarrhea, and hypothermia, accompanied by significant secretion of Th2 cytokines in the spleen and skin lymph nodes (SLN). Persistent skin barrier impairment at the lesion location exacerbated skin scratching, increased the mouse mast cell protease-1 (MCPT-1) and Th2 cytokine levels, and promoted polarization of Th2 cells in the spleen and SLN. In contrast, continuous consumption of ovalbumin water during the challenge phase alleviated diarrhea in epicutaneously sensitized FA mice, reduced the release of Th2 cytokines in the mesenteric lymph nodes (MLN), and upregulated the expression of Th1 and regulatory T cells in the MLN. These findings suggested that FA patients with impaired skin barrier should prioritize skin lesion management and may benefit from low-dose oral immunotherapy to alleviate allergic symptoms.