Impact of Skin Damage on Intestinal Immune Environment and Susceptibility to Food Allergy

Rationale: Sensitization can occur through inflamed skin, with subsequent oral exposure leading to manifestations of food allergy. Our aim was to determine whether skin injury could directly alter the immune environment of the gastrointestinal tract, facilitating sensitization by oral rather than epicutaneous allergen exposure

Methods: Balb/c, IL-4- and IL-13-reporter mice were tape stripped (TS) without allergen exposure weekly for 6 weeks. At week 7 mice were repeated challenged with 50mg of OVA. IgE was measured by ELISA and cell populations in intestinal tissues were quantified by flow cytometry and expressed as %CD45+ cells

Results: TS but not naïve mice developed diarrhea following repeated oral OVA exposure (0% vs. 47.5% naïve vs. TS, respectively), and elevated OVA-specific IgE. TS induced an increase in IL-13 production by mast cells in the small intestinal lamina propria. TS had a major impact on eosinophils in gastrointestinal lymph nodes. The frequency of activated eosinophils (SiglecF^high) increased in both the mesenteric lymph nodes (MLN) (5.2±3% vs. 20.2±2%, naïve vs. TS) and Peyer’s patch (PP)  (32±4.6% vs. 70±0.8%, naïve vs. TS); however, resting eosinophils (SiglecF^int) decreased in both the MLN (90±0.9% and 76± 2.2%, naïve and TS, respectively) and in the PP (63±3.8% vs. 27±1.1%, naïve vs. TS). Eosinophils in the MLN and PP expressed high levels of IL-4 but not IL-13. We observed increased IL-4 expression by lineage negative CD90^- cKit^int cells

Conclusions: We show that skin injury directly alters the intestinal immune environment. Injury expands Th2 cytokine-producing intestinal innate cell populations, and predisposes to oral sensitization to food allergens