TGFb1 Suppresses the Mast Cell Response In Vitro and In Vivo (86.6)

Abstract

Abstract Mast cell activation is a critical component of allergic disease, and may be regulated by cytokines present in the microenvironment. We recently described the suppressive effects of TGFb1 on IgE signaling in mouse and human mast cells. We have furthered this study, demonstrating that TGF injection or aerosolization reduces mast cell IgE receptor expression in vivo, and suppresses eosinophil recruitment in a mast cell-dependent model of airway hyperresponsiveness. We find that TGFb1 inhibits expression of the key signaling molecules Syk, Fyn, Akt, and Stat5 at the protein level without any change in mRNA expression. In contrast, expression or activation of ERK, JNK, GSK, and p38 was unaffected. Fyn transfection partially reversed TGFb1-mediated suppression of IgE-induced IL-13 secretion. Our data support the theory that TGFb1 possesses potent mast cell suppressive activities both in vitro and in vivo.