IL-9 promotes but is not necessary for systemic anaphylaxis.
Anaphylaxis represents an extreme form of allergic reaction, consisting of a sensitization phase during which allergen-specific IgE are produced and an acute effector phase triggered by allergen-induced degranulation of mast cells. We studied the role of IL-9, a Th2 cytokine implicated in asthma, in different models of murine anaphylaxis. Using a passive model of systemic anaphylaxis, in which anti-DNP IgE Abs were administered before challenge with DNP-BSA, we found that IL-9-transgenic mice or wild-type mice treated with IL-9 for 5 days were highly sensitive to fatal anaphylaxis. This effect was reproduced in both anaphylaxis-susceptible and -resistant backgrounds (FVB/N or [FVB/N x BALB/c] F(1) mice, respectively) and correlated with increased serum concentrations of mouse mast cell protease-1 level, a protein released upon mast cells degranulation. By contrast, IL-9 did not increase the susceptibility to passive cutaneous anaphylaxis. IL-9 expression also increased the susceptibility to fatal anaphylaxis when mice were sensitized by immunization against OVA before challenge with the same Ag. In this model, serum from sensitized, IL-9-transgenic mice was more potent in transferring susceptibility to OVA challenge into naive mice, indicating that IL-9 also promotes the sensitization stage. Finally, using IL-9R-deficient mice, we found that despite its anaphylaxis-promoting activity, IL-9 is dispensable for development of both passive and active anaphylaxis, at least in the C57BL/6 mouse background. Taken together, the data reported in this study indicate that IL-9 promotes systemic anaphylaxis reactions, acting at both the sensitization and effector stages, but is not absolutely required for this process.
Ludwig Institute for Cancer Research, Brussels Branch, and Experimental Medicine Unit, Université de Louvain, Brussels, Belgium.
Laurent
L
Knoops
Jamila
J
Louahed
Jacques
J
Van Snick
Jean-Christophe
JC
Renauld
D000707:Anaphylaxis / Q000201:enzymology / Q000209:etiology* / Q000276:immunology*; D000818:Animals; D053818:Chymases; D004195:Disease Models, Animal; D005260:Female; D007114:Immunization; D016906:Interleukin-9 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D010323:Passive Cutaneous Anaphylaxis / Q000276:immunology; D018123:Receptors, Interleukin / Q000172:deficiency / Q000235:genetics; D053651:Receptors, Interleukin-9; D012697:Serine Endopeptidases / Q000097:blood
D016906:Interleukin-9; D018123:Receptors, Interleukin; D053651:Receptors, Interleukin-9; D010047:Ovalbumin; D012697:Serine Endopeptidases; D053818:Chymases; C509230:Mcpt1 protein, mouse