ArticleThe FEBS journal2025
PU.1 and TGF-β signaling activate the cell-surface expression of CD103 in mast cells and dendritic cells: opposite roles of GATA2 in the expression of mucosal mast cell genes.
Article in The FEBS journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Mucosal mast cells (MMCs) are distinguished from connective tissue mast cells (MCs) by the specific cell-surface expression of integrin CD103 (also known as integrin αE/β7; αE is encoded by Itgae) and mast cell protease 1 and 2 (Mcpt1 and Mcpt2, respectively). Although the expression of the Mcpt1 and Mcpt2 genes is cooperatively regulated by the transcription factor GATA-binding protein 2 (GATA2) and transforming growth factor beta (TGF-β) signaling in MMCs, the transcriptional mechanism of the cell-surface expression of CD103 remains unknown. We herein found that surface CD103 and Itgae mRNA levels were significantly increased by the knockdown (KD) of Gata2 in mouse bone marrow-derived MCs (BMMCs), which was accelerated by TGF-β stimulation. Since the mRNA levels of Spi1 (encoding transcription factor PU.1) were increased in Gata2 KD BMMCs, we examined the effects of PU.1 on the cell-surface expression of CD103. As expected, CD103 levels on BMMCs were significantly decreased by Spi1 KD and increased by Spi1 overexpression. Spi1 KD suppressed Itgae expression even in the presence of TGF-β in BMMCs and peritoneal MCs, whereas Gata2 KD amplified the TGF-β-induced increase in Itgae expression. The amount of PU.1 binding to the cis-element in the Itgae gene was significantly and moderately increased by Gata2 KD and TGF-β stimulation, respectively. Since PU.1 is an essential transcription factor for dendritic cells (DCs), we examined the role of PU.1 in CD103 cell-surface expression on DCs. The KD experiment using bone marrow-derived DCs (BMDCs) showed a significant decrease in CD103 levels in Spi1-siRNA-transfected BMDCs. We concluded that PU.1 affected CD103 expression on MMCs and DCs by transactivating the Itgae gene, and also that GATA2, which positively regulated the MMC-specific expression of Mcpt1 and Mcpt2, inhibited the cell-surface expression of CD103 by repressing PU.1.
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