Oral Introduction of Ovalbumin Suppresses Allergic Responses Independent of Local Skin Inflammation in Epicutaneously Sensitized Mice

Early introduction of allergens is a pivotal strategy for inducing oral tolerance (OT) and preventing food allergy (FA). Given that atopic dermatitis (AD) predisposes individuals to FA through epicutaneous sensitization, we evaluated the impact of early ovalbumin (OVA) administration in epicutaneously sensitized mice with an inflamed skin. Here, early oral introduction of OVA effectively prevented FA development, characterized by significantly reduced OVA-IgE levels, suppressed mast cell activation, and systemic Th2 cytokines. Although the OT mice achieved immune tolerance, inflammation in the sensitized skin remained unaffected. Notably, we identified suppression of the intestinal mast cell gasdermin C axis, evidenced by downregulated expressions of Mcpt1, Mcpt2, Gsdmc2, and Gsdmc4. These findings confirm that early oral administration of allergens could induce OT, despite prior epicutaneous sensitization. Thus, oral allergen-induced tolerance acts as an effective regulator of the intestinal immune response and represents a promising intervention for AD patients to prevent FAs.