IL-10 enhances IgE-independent IL-33-mediated mast cell cytokine production

Abstract

Abstract IgE antibodies play a critical role in antigen-mediated mast cell activation. However, mast cells can be activated via IgE-independent mechanisms including signaling via the IL-33 receptor ST2. We have previously shown that the Th2-derived cytokine IL-10 can enhance IgE-dependent mucosal mast cell activation and promote mast cell function and survival. However, whether the effects of IL-10 on mast cells are global in nature and not limited to IgE-mediated signaling is not clear. To determine whether IL-10 can prime the activation of mast cells mediated by IgE-independent signals such as IL-33, we assessed the effects of rIL-10 exposure on IL-33-stimulated mast cells and their subsequent activation via IgE. Bone marrow-derived mast cells (BMMCs) from wild-type (WT) and IL-10−/− mice were cultured with rIL-33 with or without rIL-10 and activated with DNP-IgE and antigen. Exposure to IL-10 enhanced cytokine production in both WT and IL-10−/− BMMCs, and this was significantly increased after activation via IgE. IL-10−/−BMMCs exhibited decreased cytokine production, but this was restored upon culture with rIL-10. Interestingly, IL-33 stimulation (and subsequent activation with IgE) induced comparably enhanced levels of cytokine production, specifically IL-13 and IL-6, in both WT and IL-10−/−cells, suggesting that ST2-mediated signals can overcome the lack of IL-10. However, the addition of exogenous IL-10 to IL-33-stimulated cultures further enhanced the levels of these cytokines not only in IgE-activated cells, but also in cells stimulated with IL-33 alone. Our observations therefore suggest that IL-10 can play critical roles in enhancing mast cell function both via IgE-dependent and independent mechanisms.