Published online March 31, 2008
doi:10.1084/jem.20071046
The Journal of Experimental Medicine, Vol. 205, No. 4, 897-913
The Rockefeller University Press, 0022-1007 $30.00
© 2008 Forbes et al.
IL-9– and mast cell–mediated intestinal permeability predisposes to oral antigen hypersensitivity
Elizabeth E. Forbes1,2,
Katherine Groschwitz1,2,3,
J. Pablo Abonia1,
Eric B. Brandt1,
Elizabeth Cohen1,
Carine Blanchard1,
Richard Ahrens1,
Luqman Seidu1,
Andrew McKenzie8,
Richard Strait2,4,
Fred D. Finkelman2,9,
Paul S. Foster5,7,
Klaus I. Matthaei6,
Marc E. Rothenberg1, and
Simon P. Hogan1
1 Division of Allergy and Immunology, 2 Division of Immunobiology, 3 Graduate Program of Immunobiology, and 4 Division of Emergency Medicine, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267
5 Allergy and Inflammation Research Group and 6 Gene Targeting Group, Division of Molecular Bioscience, John Curtin School of Medical Research, Canberra 2601, Australia
7 Asthma, Allergy and Inflammation Research Centre, School of Biomedical Sciences, University of Newcastle, Newcastle, NSW 2308, Australia
8 Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 2QH, England, UK
9 Department of Medicine, Cincinnati Veterans Affair Medical Center, Cincinnati, OH 45220
CORRESPONDENCE Simon P. Hogan: simon.hogan{at}cchmc.org
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.
Abbreviations used: CAE, chloroacetate esterase; CMF, calcium- and magnesium-free; GI, gastrointestinal; hGH, human growth hormone; IBD, inflammatory bowel disease; i.g., intragastric; Isc, short-circuit current; MLN, mesenteric LN; MNC, mononuclear cell; VL, vascular leakage.
E.E. Forbes and K. Groschwitz contributed equally to this paper.
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