Title: TGF-β-induced suppression of mast cell functions is mediated by the transcription factor Ehf
Abstract: Mast cells act as the major effector cells in allergic skin inflammation. Transforming growth factor (TGF)-β1 inhibits the effector functions, in part, by decreasing mast cell surface expression of the high affinity IgE receptor (FcɛRI) and stem cell factor receptor c-Kit. However, the molecular mechanism by which these expressions are decreased by TGF-β1 remains unclear. In this study, we found that the expression of Ets homologous factor (Ehf), a member of the Ets family of transcriptional factors, is significantly up-regulated in mouse bone marrow-derived mast cells (BMMCs) treated with TGF-β1. Functionally, Ehf is predicted to be a transcriptional repressor of several genes. Thus, we investigated the effect of Ehf on FcɛRI and c-Kit expression and cell activation. Forced expression of Ehf in BMMCs resulted in a significant decrease in the cell surface expressions of FcɛRI and c-Kit in the absence of TGF-β1. Ehf repressed the transcription of genes encoding c-Kit, FcɛRIα subunit, and FcɛRIβ subunit, but not FcɛRIγ subunit. Furthermore, forced expression of Ehf suppressed mast cell degranulation and cytokine production induced by FcɛRI cross-linking. The mRNA levels of transcription factors Gata1 and Gata2, which are positive regulators of the transcription of genes encoding FcɛRIα, FcɛRIβ, and c-Kit, and Stat5b, which is a critical regulator of cytokine induction, were lower in Ehf-expressing BMMCs compared with control cells. These results indicate that TGF-β1 suppresses FcɛRI and c-Kit expression, and suppresses FcɛRI-mediated activation, through up-regulation of Ehf in mast cells.
Publication Year: 2016
Publication Date: 2016-10-01
Language: en
Type: article
Indexed In: ['crossref']
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