IL-10 Can Enhance FcγR-mediated Mast Cell Activation

Abstract

Abstract Mast cells are involved in many inflammatory diseases, partly by their production of cytokines that promote inflammation. IgG signaling through FcγRIII/IIb in mast cells is linked to autoimmune disease such as rheumatoid arthritis, but factors controlling this signaling remain unclear. Our group, as well as others, has previously shown that IL-10 suppresses mast cell IgE signaling, consistent with known anti-inflammatory effects of IL-10. However, we recently found that in IL-10 has unexpected pro-inflammatory effects on IgE-mediated mast cell functions. Therefore, we designed a study to determine the effects of IL-10 on FcγR signaling. Our data show that IL-10 enhances IgG-mediated IL-6 and MCP-1 production in bone marrow derived mast cells. Interestingly, we also found that IgG-induced cytokine production is suppressed by IL-10 in bone marrow derived macrophages under the same conditions. Current work is examining this different response to IL-10 to have a better understanding of the overall affect of IL-10 in the inflamed microenvironment. These studies suggest that mast cell and macrophage responses are altered by cytokines in their microenvironment, with distinct and opposite effects.