Gene expression profile of mature plasmacytoid dendritic cells (PDC) after the deletion of transcription factor E2-2

The interferon-producing plasmacytoid dendritic cells (PDC) share common progenitors with antigen-presenting classical dendritic cells (cDC), yet they possess distinct morphology and molecular features resembling those of lymphocytes. It is unclear whether the unique cell fate of PDC is actively maintained in the steady state. We report that the deletion of transcription factor E2-2 from mature peripheral PDC caused their spontaneous differentiation into cells with cDC properties. This included the loss of PDC markers, increase in MHC class II expression and T cell priming capacity, acquisition of dendritic morphology and induction of cDC signature genes. Genome-wide chromatin immunoprecipitation revealed direct binding of E2-2 to key PDC-specific and lymphoid genes, as well as to certain genes enriched in cDC. Thus, E2-2 actively maintains the cell fate of mature PDC and opposes the default cDC fate, in part through direct regulation of lineage-specific gene expression programs.

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