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

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.
Authors	Elizabeth E Forbes, Katherine Groschwitz, J Pablo Abonia, Eric B Brandt, Elizabeth Cohen, Carine Blanchard, Richard Ahrens, Luqman Seidu, Andrew McKenzie, Richard Strait, Fred D Finkelman, Paul S Foster, Klaus I Matthaei, Marc E Rothenberg, Simon P Hogan
Journal	The Journal of experimental medicine (J Exp Med) Vol. 205 Issue 4 Pg. 897-913 (Apr 14 2008) ISSN: 1540-9538 [Electronic] United States
PMID	18378796 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antigens Fatty Acid-Binding Proteins Interleukin-9 Receptors, Interleukin-4 STAT6 Transcription Factor Ovalbumin Cromolyn Sodium
Topics	Administration, Oral Anaphylaxis (chemically induced, genetics) Animals Antigens (administration & dosage, pharmacology) Cromolyn Sodium (pharmacology) Disease Susceptibility (immunology) Fatty Acid-Binding Proteins (genetics) Gene Expression Profiling Hypersensitivity (immunology) Interleukin-9 (deficiency, immunology) Intestines (drug effects, immunology) Mast Cells (immunology) Mastocytosis (immunology) Mice Mice, Transgenic Ovalbumin (administration & dosage, pharmacology) Permeability (drug effects) Phenotype Rats Receptors, Interleukin-4 (metabolism) STAT6 Transcription Factor (metabolism) Th2 Cells (immunology)

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