Exposure to food allergens through inflamed skin promotes intestinal food allergy through the thymic stromal lymphopoietin-basophil axis

J Allergy Clin Immunol. 2014 May;133(5):1390-9, 1399.e1-6. doi: 10.1016/j.jaci.2014.01.021. Epub 2014 Feb 20.

Abstract

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 T(H)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 T(H)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.

Keywords: Food allergy; IgE; atopic dermatitis; basophils; epicutaneous sensitization; mast cells; thymic stromal lymphopoietin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / immunology*
  • Animals
  • Basophils / immunology*
  • Basophils / pathology
  • Cytokines / genetics
  • Cytokines / immunology*
  • Dermatitis, Atopic / complications
  • Dermatitis, Atopic / genetics
  • Dermatitis, Atopic / immunology*
  • Dermatitis, Atopic / pathology
  • Food Hypersensitivity / etiology
  • Food Hypersensitivity / genetics
  • Food Hypersensitivity / immunology*
  • Food Hypersensitivity / pathology
  • Immunoglobulin E / genetics
  • Immunoglobulin E / immunology
  • Intestinal Mucosa / metabolism
  • Intestines / immunology*
  • Mast Cells / immunology
  • Mast Cells / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Skin / immunology
  • Skin / pathology
  • Th2 Cells / immunology
  • Th2 Cells / pathology

Substances

  • Allergens
  • Cytokines
  • Immunoglobulin E
  • thymic stromal lymphopoietin