The ETS Transcription Factor Spi-B Is Required for Human Plasmacytoid Dendritic Cell Development

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Abstract
A number of transcription factors that act as molecular switches for hematopoietic lineage decisions have been identified. We recently described the ETS transcription factor Spi-B to be exclusively expressed in plasmacytoid dendritic cells (pDCs), but not in myeloid DCs. To assess whether Spi-B is required for pDC development we used an RNA interference knock down approach to specifically silence Spi-B protein synthesis in CD34+ precursor cells. We observed that a knock down of Spi-B mRNA strongly inhibited the ability of CD34+ precursor cells to develop into pDCs in both in vitro assays as well as in vivo upon injection into recombination activating gene 2−/− γ common−/− mice. The observed effects were restricted to the pDC lineage as the differentiation of pro–B cells and CD14+ myeloid cells was not inhibited but slightly elevated by Spi-B knock down. Knock down of the related ETS factor PU.1 also inhibited in vitro development of CD34+ cells into pDCs. However, in contrast to Spi-B, PU.1 knock down inhibited B cell and myeloid cell development as well. These results identify Spi-B as a key regulator of human pDC development.