TGF-β1 Inhibits Mast Cell FcεRI Expression

Abstract

Mast cell activation through the high affinity IgE receptor (FcεRI) is a critical component of atopic inflammation. The cytokine TGF-β1 has been shown to inhibit IgE-dependent mast cell activation, possibly serving to dampen mast cell-mediated inflammatory responses. We present proof that TGF-β1 inhibits mast cell FcεRI expression through a reversible pathway that diminishes protein, but not mRNA, expression of the FcεRI subunit proteins α, β, and γ. The stability of the expressed proteins and the assembled cell surface complex was unaltered by TGF-β1 treatment. However, TGF-β1 decreased the rate of FcεRI β-chain synthesis, arguing that this inhibitory cytokine exerts its effects at the level of mRNA translation. TGF-β1 consistently diminished FcεRI expression on cultured human or mouse mast cells as well as freshly isolated peritoneal mast cells. The related cytokines, TGF-β2 and TGF-β3, had similar effects. We propose that TGF-β1 acts as a negative regulator of mast cell function, in part by decreasing FcεRI expression.