期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 133, 期 5, 页码 1390-U643出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2014.01.021
关键词
Food allergy; atopic dermatitis; epicutaneous sensitization; thymic stromal lymphopoietin; basophils; mast cells; IgE
资金
- National Institutes of Health [AI061570, AI087990, AI074878, AI106679, AI095466, AI095608, AI102942, AI097333]
- Crohn's and Colitis Foundation of America
- Burroughs Wellcome Fund Investigator in Pathogenesis of Infectious Disease Award
- Swiss National Science Foundation Prospective and Advanced Research Fellowships [PBBEP3_130438, PA00P3_136468]
- Swiss National Science Foundation (SNF) [PBBEP3_130438, PA00P3_136468] Funding Source: Swiss National Science Foundation (SNF)
- Medical Research Council [G0000635] Funding Source: researchfish
- MRC [G0000635] Funding Source: UKRI
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.
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