Anatomical Site and Extent of Intestinal Epithelial Injury Affect Oral Sensitization to Ovalbumin in Rats

Nonsteroidal anti-inflammatory drugs have been reported to enhance oral sensitization to food allergens, potentially through disruption of the intestinal epithelial barrier. Epithelial-derived cytokines, including thymic stromal lymphopoietin (TSLP), interleukin (IL)-33, and IL-25, promote immunoglobulin E (IgE) production by inducing T helper type 2 immune responses and may contribute to allergen sensitization following epithelial injury. This study aimed to investigate oral sensitization to ovalbumin (OVA) in a rat model of intestinal epithelial injury induced by dextran sulfate sodium (DSS) or indomethacin (IND), focusing on the involvement of TSLP in relation to the anatomical site of epithelial injury. Rats were orally immunized with OVA by gavage every other day for 6 weeks. DSS was administered in drinking water from 2 weeks before immunization, whereas IND was administered orally at a dose of 6 mg/kg 30 min before each OVA administration. To explore the involvement of TSLP, anti-TSLP antibodies were administered intraperitoneally once a week throughout the immunization period. Histological analysis showed that DSS induced epithelial injury in both the jejunum and proximal colon, whereas IND caused milder epithelial injury limited to the jejunum. Plasma OVA-specific IgE (OVA-sIgE) levels were elevated in both models. Anti-TSLP antibody treatment attenuated DSS-enhanced OVA-sIgE production, but had limited effects in the IND model. In conclusion, intestinal epithelial injury may enhance oral sensitization through mechanisms that differ according to the anatomical site and extent of injury. TSLP appears to contribute predominantly to sensitization associated with epithelial damage involving both the jejunum and proximal colon.