Differential Expression of the Transcription Factor SPI1 (PU.1) in Dendritic Cell Subsets

Abstract

Abstract SPI1 belongs to the E26-transformation-specific (Ets) family of transcription factors and is exclusively expressed in hematopoietic cells. Originally identified as an oncogene that blocks erythroblast differentiation, SPI1 plays a critical role in the development and lineage commitment of both myeloid and lymphoid cells. Gene knockout studies show that spi1−/− mice exhibit a multi-lineage defect in the generation of monocytes, granulocytes, B, T, and dendritic cells. While SPI1 expression is required for normal hematopoietic cell development, the level of SPI1 expression influences specific lineage commitment. Using in-house generated species-specific clones, human peripheral blood mononuclear cells (PMBCs) and mouse splenocytes were evaluated for SPI1 expression by flow cytometric analysis. In human PMBCs, Lin− HLA-DR+ CD11c+ CD303− monocyte-derived dendritic cells (mDCs) exhibit high levels of expression while Lin− HLA-DR+ CD11cint CD303+ plasmacytoid dendritic cells (pDCs) do not express SPI1 protein. These data suggest SPI1 expression is required for the development and function of human mDCs, while SPI1 expression is not necessary for terminally differentiated human pDCs. Interestingly, SPI1 expression is detected in both murine DC subsets: Lin− I-A/I-E+ CD11c+ CD317− mDCs and Lin− I-A/I-E+ CD11cint CD317+ pDCs, although the expression level in pDCs is significantly lower than in mDCs. These observations indicate expression patterns differ between mouse and human cells, and demonstrate that DC subsets exhibit differential expression of SPI1 protein.