Differential roles for the IL-9/IL-9 receptor alpha-chain pathway in systemic and oral antigen-induced anaphylaxis.

Abstract

BACKGROUND:

The cytokine IL-9 has been implicated in allergic reactions, including food allergy, but its contribution to parenteral versus oral antigen-induced anaphylaxis remains unclear.

OBJECTIVES:

We sought to delineate the contribution of the IL-9/IL-9 receptor alpha-chain (IL-9R) pathway to parenteral and oral antigen-induced anaphylaxis.

METHODS:

Wild-type, IL-9-deficient (Il9(-/-)), and IL-9R-deficient (Il9R(-/-)) mice were subjected to passive and active parenteral and oral antigen (ovalbumin [OVA])-induced anaphylaxis. Severity of systemic anaphylaxis was gauged by decreased body temperature; intestinal anaphylaxis was assessed based on secretory diarrhea, intestinal mastocytosis, and serum murine mast cell protease 1 level. Specific immunoglobulin isotypes or immunoglobulin receptor-blocking antibodies were administered before challenge to define the role of the IgE and IgG pathways.

RESULTS:

Repeated oral antigen challenge of OVA-sensitized wild-type mice induced anaphylaxis with both systemic and intestinal involvement; both were IgE dependent and attenuated in Il9(-/-) and Il9R(-/-) mice. In contrast, parenteral OVA challenge of OVA-sensitized wild-type mice induced systemic anaphylaxis, which was independent of the IL-9/IL-9R pathway. Strikingly, the IL-9/IL-9R pathway had no role in either the IgG or IgE component of parenteral antigen-induced or anti-IgE and anti-FcgammaRII/III mAb-induced systemic anaphylaxis.

CONCLUSIONS:

Parenteral antigen-induced murine systemic anaphylaxis is mediated by both IgG- and IgE-dependent pathways, and both can occur independently of IL-9/IL-9R signaling. In contrast, oral antigen-induced intestinal and systemic anaphylaxis is strictly IgE mediated and requires IL-9/IL-9R signaling. These studies indicate differential involvement of the IL-9/IL-9R pathway in systemic and oral antigen-induced anaphylaxis.

• Authors: Heather Osterfeld, Richard Ahrens, Richard Strait, Fred D Finkelman, Jean-Christophe Renauld, Simon P Hogan
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 125 Issue 2 Pg. 469-476.e2 (Feb 2010) ISSN: 1097-6825 [Electronic] United States
• PMID: 20159257 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Chemical References

• Immunoglobulin G
• Interleukin-9
• Receptors, Interleukin-9
• Immunoglobulin E
• Ovalbumin

Topics

• Anaphylaxis (chemically induced, immunology)
• Animals
• Enzyme-Linked Immunosorbent Assay
• Immunoglobulin E (immunology)
• Immunoglobulin G (immunology)
• Infusions, Parenteral
• Interleukin-9 (immunology)
• Intestines (immunology)
• Mast Cells (immunology)
• Mice
• Mice, Knockout
• Ovalbumin (administration & dosage, adverse effects, immunology)
• Receptors, Interleukin-9 (immunology)
• Signal Transduction (immunology)