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

TitleExposure to food allergens through inflamed skin promotes intestinal food allergy through the thymic stromal lymphopoietin-basophil axis.
Publication TypeJournal Article
Year of Publication2014
AuthorsNoti, M, Kim, BS, Siracusa, MC, Rak, GD, Kubo, M, Moghaddam, AE, Sattentau, QA, Comeau, MR, Spergel, JM, Artis, D
JournalJ Allergy Clin Immunol
Volume133
Issue5
Pagination1390-9, 1399.e1-6
Date Published2014 May
ISSN1097-6825
KeywordsAllergens, Animals, Basophils, Cytokines, Dermatitis, Atopic, Food Hypersensitivity, Immunoglobulin E, Intestines, Mast Cells, Mice, Mice, Inbred BALB C, Mice, Knockout, Skin, Th2 Cells
Abstract

<p>BACKGROUND: Exposure to food allergens through a disrupted skin barrier has been recognized as a potential factor in the increasing prevalence of food allergy.</p><p>OBJECTIVE: We sought to test the immunologic mechanisms by which epicutaneous sensitization to food allergens predisposes to intestinal food allergy.</p><p>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.</p><p>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.</p><p>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.</p>

DOI10.1016/j.jaci.2014.01.021
Alternate JournalJ. Allergy Clin. Immunol.
PubMed ID24560412
PubMed Central IDPMC4007098
Grant List2-P30- CA016520 / CA / NCI NIH HHS / United States
AI061570 / AI / NIAID NIH HHS / United States
AI074878 / AI / NIAID NIH HHS / United States
AI087990 / AI / NIAID NIH HHS / United States
AI095466 / AI / NIAID NIH HHS / United States
AI095608 / AI / NIAID NIH HHS / United States
AI097333 / AI / NIAID NIH HHS / United States
AI102942 / AI / NIAID NIH HHS / United States
AI106679 / AI / NIAID NIH HHS / United States
F32-AI085828 / AI / NIAID NIH HHS / United States
KL2-RR024132 / RR / NCRR NIH HHS / United States
P01 AI106697 / AI / NIAID NIH HHS / United States
P30 AR057217 / AR / NIAMS NIH HHS / United States
P30-DK050306 / DK / NIDDK NIH HHS / United States
R01 AI061570 / AI / NIAID NIH HHS / United States
R01 AI074878 / AI / NIAID NIH HHS / United States
R01 AI095466 / AI / NIAID NIH HHS / United States
R01 AI097333 / AI / NIAID NIH HHS / United States
R01 AI102942 / AI / NIAID NIH HHS / United States
R21 AI083480 / AI / NIAID NIH HHS / United States
R21 AI087990 / AI / NIAID NIH HHS / United States
T32-AR007465 / AR / NIAMS NIH HHS / United States
U01 AI095608 / AI / NIAID NIH HHS / United States