IL-10 enhances mast cell activation and is essential for the development of IgE-mediated experimental food allergy

Abstract

Abstract IL-10 is a key pleiotropic cytokine that can both promote and curb Th2-dependent allergic responses. Herein we demonstrate a novel role for IL-10 in the development of IgE-mediated food allergy. Oral ovalbumin challenge in sensitized BALB/c mice resulted in a robust intestinal mast cell response accompanied by allergic diarrhea, mast cell activation and a predominance of Th2 cytokines, including enhanced IL-10 expression. In contrast, the development of intestinal anaphylaxis including diarrhea, mast cell activation, and Th2 cytokine production was significantly attenuated in IL-10−/− mice compared to WT controls. Furthermore, IL-10 directly promoted the activation of mast cells. Administration of IgE and antigen induced the development of passive anaphylaxis in WT mice, which was attenuated in IL-10−/− animals. However, treatment of IL-10−/− mice with recombinant IL-10 prior to IgE administration restored the development of passive anaphylaxis in these animals. Finally, adoptive transfer of WT mast cells restored allergic symptoms in IL-10−/− mice. Our observations demonstrate a critical role for IL-10 in driving mucosal mast cell activation, suggesting that in its absence, mast cell function is impaired, leading to attenuated food allergy symptoms.