First Author | Osterfeld H | Year | 2010 |
Journal | J Allergy Clin Immunol | Volume | 125 |
Issue | 2 | Pages | 469-476.e2 |
PubMed ID | 20159257 | Mgi Jnum | J:183369 |
Mgi Id | MGI:5318463 | Doi | 10.1016/j.jaci.2009.09.054 |
Citation | Osterfeld H, et al. (2010) Differential roles for the IL-9/IL-9 receptor alpha-chain pathway in systemic and oral antigen-induced anaphylaxis. J Allergy Clin Immunol 125(2):469-476.e2 |
abstractText | 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. |