Atopic dermatitis- like skin inflammation promotes skin sensitisation to enzyme- hydrolysed gluten proteins and alters systemic immune function in brown norway rats

Background: Atopic dermatitis (AD) is associated with the development of food allergy and increased risk for infections. Here we studied the cutaneous sensitisation to enzyme- hydrolysed gluten (EHG) proteins in a model of AD in Brown Norway rats. Alterations in systemic immune function were investigated to reveal underlying drives of AD associated comorbidities. Method: Brown Norway rats were kept on a wheat- free diet for more than 10 generations. AD- like skin inflammation was induced by the application of vitamin D3 analogue MC903 to shaved abdominal skin. EHG were applied to the abdominal skin for 1 hour, 3 times/week for 5 weeks to induce sensitisation. Allergic sensitisation was assessed by measurements of EHG specific- IgE in serum, ear swelling test, and clinical symptoms after oral challenge with EHG. T cell phenotypes and inflammatory cells were analysed in the skin, blood, peritoneal cavity, and intestine by flow cytometry. The immune response to bacterial lysates, food allergens, and M1/M2- polarising cytokines was analysed by stimulation of peritoneal- derived macrophages. Intestinal permeability was evaluated by protein uptake in intestinal epithelium, lamina propria, Peyer’s patches, and serum. Results: AD was found to promote sensitisation to EHG via the skin. Increased AD- mediated skin sensitization was associated with an ncreased ear swelling response to EHG, and increased numbers of clinical symptoms following oral challenge with EHG. AD had little effect on the composition of immune cells in the blood, peritoneal cavity, and intestine. Peritoneal macrophages derived from of rats with AD exhibited alterations in the response to bacterial lysates compared to macrophages from rats without skin inflammation. AD was associated with altered protein uptake in the intestine. Conclusion: AD promotes skin sensitisation and allergic responses to wheat- derived food allergen. Our findings indicate that AD drives alterations in systemic immune function and intestinal permeability, which could increase the risk for AD- associated comorbidities.