IL-9– and mast cell–mediated intestinal permeability predisposes to oral antigen hypersensitivity

Author:

Forbes Elizabeth E.12,Groschwitz Katherine123,Abonia J. Pablo1,Brandt Eric B.1,Cohen Elizabeth1,Blanchard Carine1,Ahrens Richard1,Seidu Luqman1,McKenzie Andrew4,Strait Richard25,Finkelman Fred D.26,Foster Paul S.78,Matthaei Klaus I.9,Rothenberg Marc E.1,Hogan Simon P.1

Affiliation:

1. Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267

2. Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267

3. Graduate Program of Immunobiology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267

4. Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 2QH, England, UK

5. Division of Emergency Medicine, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267

6. Department of Medicine, Cincinnati Veterans Affair Medical Center, Cincinnati, OH 45220

7. Allergy and Inflammation Research Group, John Curtin School of Medical Research, Canberra 2601, Australia

8. Asthma, Allergy and Inflammation Research Centre, School of Biomedical Sciences, University of Newcastle, Newcastle, NSW 2308, Australia

9. Gene Targeting Group, Division of Molecular Bioscience, John Curtin School of Medical Research, Canberra 2601, Australia

Abstract

Previous mouse and clinical studies demonstrate a link between Th2 intestinal inflammation and induction of the effector phase of food allergy. However, the mechanism by which sensitization and mast cell responses occurs is largely unknown. We demonstrate that interleukin (IL)-9 has an important role in this process. IL-9–deficient mice fail to develop experimental oral antigen–induced intestinal anaphylaxis, and intestinal IL-9 overexpression induces an intestinal anaphylaxis phenotype (intestinal mastocytosis, intestinal permeability, and intravascular leakage). In addition, intestinal IL-9 overexpression predisposes to oral antigen sensitization, which requires mast cells and increased intestinal permeability. These observations demonstrate a central role for IL-9 and mast cells in experimental intestinal permeability in oral antigen sensitization and suggest that IL-9–mediated mast cell responses have an important role in food allergy.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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