IL-9 Promotes but Is Not Necessary for Systemic Anaphylaxis

Abstract

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 × BALB/c] F1 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.

T helper 9 cells induced by plasmacytoid dendritic cells regulate interleukin-17 in multiple sclerosis

“…On the other hand, IL-9 is a cytokine implicated in human and murine asthma, anaphylaxis, resistance to nematode infection, antiviral immunity and tumorigenesis [60][61][62][63][64][65][66][67][68][69]. The role of IL-9 in autoimmunity has been investigated in the mouse model of MS, experimental autoimmune encephalomyelitis (EAE).…”

IL-13 Mediates In Vivo IL-9 Activities on Lung Epithelial Cells but Not on Hematopoietic Cells

“…Interestingly, this mast cell-stimulating role of IL-9 appears to be the less redundant activity of this cytokine as IL-9-deficient mice show a defective mastocytosis in a pulmonary granuloma model (16), although IL-9 is not required for other mast cell-dependent processes such as systemic anaphylaxis (44).…”

Elevated serum cytokines during human anaphylaxis: Identification of potential mediators of acute allergic reactions

“…4 IL-9 promotes mast cell differentiation, B-cell activation, eosinophilia, and mucus production by lung epithelial cells. 5 We also measured MCT and histamine because these are well established to correlate with reaction severity in human beings. 6,7 …”