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.
Knoops
Laurent
L
Ludwig Institute for Cancer Research, Brussels Branch, and Experimental Medicine Unit, Université de Louvain, Brussels, Belgium.
Louahed
Jamila
J
Van Snick
Jacques
J
Renauld
Jean-Christophe
JC
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