IL-33-induced activation of human basophils and eosinophils via ST2

Abstract

Objective: A cytokine of the IL-1 family, IL-33, has recently been recognized as one of the key cytokines enhancing Th2-balanced immune regulation through its receptor, ST2. However, the action of IL-33 on aller- gic effector granulocytes has remained unclear. We thus tested whether IL-33 acts directly on, and affects the functions of, human basophils and eosinophils. Methods: Basophils and eosinophils were prepared from normal human peripheral blood. Cells were treated with IL-33, and their adhesion, migration, surface CD11b expression, mediator release and survival were assessed in vitro. Expression of ST2 was analyzed at both the mRNA and protein levels. Results: Analysis by real-time PCR and flow cytometry demonstrated that both basophils and eosinophils expressed mRNA and protein for ST2. Expressions of IL-4 and IL-13 mRNA in basophils were upregulated by IL-33. IL-33 at 1-100 ng/ml potently enhanced the adhesiveness and CD11b expression of basophils and eosinophils. Although IL-33 failed to directly induce degranulation or migration of basophils, it exerted prim- ing effects by enhancing basophil migration toward eotaxin and degranulation in response to IgE-crosslinking stimulus. IL-33 prolonged survival of eosinophils, but not basophils, via suppression of their apoptosis. In addition, blocking of ST2 with neutralizing antibody inhibited IL-33-induced upregulation of basophil and eosinophil functions. Conclusion: IL-33 is a potent regulator of various functions of basophils and eosinophils. IL-33 may be a key cytokine in the pathogenesis of Th2-dominant allergic diseases, at least partly by acting on effector cells, including basophils and eosinophils. Rec: