Background Exposure to food allergens through a disrupted skin barrier has been recognized as a potential factor in the increasing prevalence of food allergy. Objective We sought to test the ...immunologic mechanisms by which epicutaneous sensitization to food allergens predisposes to intestinal food allergy. Methods Mice were epicutaneously sensitized with ovalbumin or peanut on an atopic dermatitis–like skin lesion, followed by intragastric antigen challenge. Antigen-specific serum IgE levels and TH 2 cytokine responses were measured by ELISA. Expression of type 2 cytokines and mast cell proteases in the intestine were measured by using real-time PCR. Accumulation of basophils in the skin and mast cells in the intestine was examined by using flow cytometry. In vivo basophil depletion was achieved by using diphtheria toxin treatment of Baso-DTR mice. For cell-transfer studies, the basophil population was expanded in vivo by means of hydrodynamic tail vein injection of thymic stromal lymphopoietin (TSLP) cDNA plasmid. Results Sensitization to food allergens through an atopic dermatitis–like skin lesion is associated with an expansion of TSLP-elicited basophils in the skin that promote antigen-specific TH 2 cytokine responses, increased antigen-specific serum IgE levels, and accumulation of mast cells in the intestine, promoting the development of intestinal food allergy. Critically, disruption of TSLP responses or depletion of basophils reduced the susceptibility to intestinal food allergy, whereas transfer of TSLP-elicited basophils into intact skin promoted disease. Conclusion Epicutaneous sensitization on a disrupted skin barrier is associated with accumulation of TSLP-elicited basophils, which are necessary and sufficient to promote antigen-induced intestinal food allergy.
...phenotypic and cytokine profile analyses of peanut-pulsed BMDCs revealed no classical activation by raw or DR peanut preparations compared with LPS (Fig 2, D and E, and see Fig E7 in this ...article's Online Repository at www.jacionline.org). ...by contrast with direct AGE-relevant modification of HEL that showed increased presentation to an HEL-specific T-cell hybridoma, DR PPE-pulsed dendritic cells (DCs) did not enhance the presentation of unmodified HEL, reinforcing the absence of DR PPE-elicited DC costimulation (Fig 2, F, and see Fig E8 in this article's Online Repository at www.jacionline.org).
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