Mario Noti1, Brian S Kim2, Mark C Siracusa3, Gregory D Rak3, Masato Kubo4, Amin E Moghaddam5, Quentin A Sattentau5, Michael R Comeau6, Jonathan M Spergel7, David Artis8. 1. Department of Microbiology, University of Pennsylvania, Philadelphia, Pa; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pa; Division of Experimental Pathology, Institute of Pathology, University of Bern, Bern, Switzerland. 2. Department of Microbiology, University of Pennsylvania, Philadelphia, Pa; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pa; Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pa. 3. Department of Microbiology, University of Pennsylvania, Philadelphia, Pa; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pa. 4. Laboratory for Cytokine Regulation, Research Center for Integrative Medical Science, RIKEN Yokohama Institute, Kanagawa, Japan; Division of Molecular Pathology, Research Institute for Biomedical Science, Tokyo University of Science, Chiba, Japan. 5. Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom. 6. Inflammation Research, Amgen, Seattle, Wash. 7. Department of Pediatrics, Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, Pa. 8. Department of Microbiology, University of Pennsylvania, Philadelphia, Pa; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pa; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pa. Electronic address: dartis@mail.med.upenn.edu.
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.
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.
Authors: Baohua Zhou; Michael R Comeau; Thibaut De Smedt; H Denny Liggitt; Martin E Dahl; David B Lewis; Dora Gyarmati; Theingi Aye; Daniel J Campbell; Steven F Ziegler Journal: Nat Immunol Date: 2005-09-04 Impact factor: 25.606
Authors: Mario Noti; Elia D Tait Wojno; Brian S Kim; Mark C Siracusa; Paul R Giacomin; Meera G Nair; Alain J Benitez; Kathryn R Ruymann; Amanda B Muir; David A Hill; Kudakwashe R Chikwava; Amin E Moghaddam; Quentin J Sattentau; Aneesh Alex; Chao Zhou; Jennifer H Yearley; Paul Menard-Katcher; Masato Kubo; Kazushige Obata-Ninomiya; Hajime Karasuyama; Michael R Comeau; Terri Brown-Whitehorn; Rene de Waal Malefyt; Patrick M Sleiman; Hakon Hakonarson; Antonella Cianferoni; Gary W Falk; Mei-Lun Wang; Jonathan M Spergel; David Artis Journal: Nat Med Date: 2013-07-21 Impact factor: 53.440
Authors: Brian S Kim; Kelvin Wang; Mark C Siracusa; Steven A Saenz; Jonathan R Brestoff; Laurel A Monticelli; Mario Noti; Elia D Tait Wojno; Thomas C Fung; Masato Kubo; David Artis Journal: J Immunol Date: 2014-08-25 Impact factor: 5.422
Authors: L Tordesillas; N Cubells-Baeza; C Gómez-Casado; C Berin; V Esteban; W Barcik; L O'Mahony; C Ramirez; L F Pacios; M Garrido-Arandia; A Díaz-Perales Journal: Clin Exp Allergy Date: 2017-07-14 Impact factor: 5.018