TGFβ inhibits IL-33-mediated mast cell activation in vitro and in vivo

TGFβ is involved in many pathological conditions, including autoimmune disorders, cancer, and cardiovascular and allergic diseases. We have previously found that TGFβ suppresses IgE-mediated mast cell activation in human and mouse mast cells in vitro . IL-33 is a recently discovered member of the IL-1 family that functions as an “alarmin” stimulating mast cell responses and enhancing IgE-mediated activation. How TGFβ affects IL-33 signaling is now known. We find that mouse bone marrow-derived mast cells cultured in TGFβ -1, -2, or -3 showed reduced IL-33-mediated production of TNF, IL-6, IL-13 and MCP-1, in a concentration-dependent manner. Furthermore, TGFβ also reduced expression of the IL-33 receptor ST2, as well as IL-33-mediated TAK1, IKB and ERK phosphorylation. TGF-β 1 injection suppressed IL-33-mediated production of systemic inflammatory cytokines in vivo. The role of IL-33 in the pathogenesis of allergic diseases is incompletely understood. These findings, consistent with our previously reported effects of TGFβ on IgE-mediated activation, demonstrate that TGFβ can provide broad and substantial inhibitory signals to activated mast cells. These data suggest possible therapeutic strategies to maintain mast cell homeostasis in autoimmune and allergic diseases.