IL-9- and mast cell-mediated intestinal permeability predisposes to oral antigen hypersensitivity.
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.
Forbes
Elizabeth E
EE
Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, USA.
Groschwitz
Katherine
K
Abonia
J Pablo
JP
Brandt
Eric B
EB
Cohen
Elizabeth
E
Blanchard
Carine
C
Ahrens
Richard
R
Seidu
Luqman
L
McKenzie
Andrew
A
Strait
Richard
R
Finkelman
Fred D
FD
Foster
Paul S
PS
Matthaei
Klaus I
KI
Rothenberg
Marc E
ME
Hogan
Simon P
SP
D000284:Administration, Oral; D000707:Anaphylaxis / Q000139:chemically induced / Q000235:genetics; D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000494:pharmacology*; D004205:Cromolyn Sodium / Q000494:pharmacology; D004198:Disease Susceptibility / Q000276:immunology; D050556:Fatty Acid-Binding Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D006967:Hypersensitivity / Q000276:immunology*; D016906:Interleukin-9 / Q000172:deficiency / Q000276:immunology*; D007422:Intestines / Q000187:drug effects / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology*; D008415:Mastocytosis / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000494:pharmacology; D010539:Permeability / Q000187:drug effects; D010641:Phenotype; D051381:Rats; D019948:Receptors, Interleukin-4 / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology
D000941:Antigens; D050556:Fatty Acid-Binding Proteins; D016906:Interleukin-9; D019948:Receptors, Interleukin-4; D050800:STAT6 Transcription Factor; D010047:Ovalbumin; D004205:Cromolyn Sodium