IL-33 induces IL-13 production by mouse mast cells independently of IgE-FcεRI signals

The IL-1-related molecules, IL-1 and IL-18, can promote Th2 cytokine production by IgE/antigen-Fc epsilon RI-stimulated mouse mast cells. Another IL-1-related molecule, IL-33, was identified recently as a ligand for T1/ST2. Although mouse mast cells constitutively express ST2, the effects of IL-33 on mast cell function are poorly understood. We found that IL-33, but not IL-1 beta or IL-18, induced IL-13 and IL-6 production by mouse bone marrow-derived, cultured mast cells (BMCMCs) independently of IgE. In BMCMCs incubated with the potently cytokinergic SPE-7 IgE without specific antigen, IL-33, IL-1 beta,and IL- 18 each promoted IL- 13 and IL- 6 production, but the effects of IL- 33 were more potent than those of IL-1 beta or IL-18. IL- 33 promoted cytokine production via a MyD88-dependent but Toll/IL-1R domain-containing adaptor-inducing IFN-beta-independent pathway. By contrast, IL- 33 neither induced nor enhanced mast cell degranulation. At 200 ng/ ml, IL- 33 prolonged mast cell survival in the absence of IgE and impaired survival in the presence of SPE-7 IgE, whereas at 100 ng/ ml, IL- 33 had no effect on mast cell survival in the absence of IgE and reduced mast cell survival in the presence of IgE. These observations suggest potential roles for IL- 33 in mast cell- and Th2 cytokine-associated immune responses and disorders.