Identification of CCR9− murine plasmacytoid DC precursors with plasticity to differentiate into conventional DCs

Whereas the final differentiation of conventional dendritic cells (CDCs) from committed precursors occurs locally in secondary lymphoid or peripheral tissues, plasmacytoid dendritic cells (PDCs) are thought to fully develop in the bone marrow from common DC progenitors before migrating to the periphery. In our study, we define, for the first time, a subpopulation of CCR9− major histocompatibility complex class IIlow PDCs in murine bone marrow, which express E2-2 and are immediate precursors of CCR9+ fully differentiated PDCs. However, CCR9− PDCs have the plasticity to acquire the phenotype and function of CD11b+ CD8α− major histocompatibility complex class IIhigh CDC-like cells under the influence of soluble factors produced by intestinal epithelial cells or recombinant GM-CSF. This deviation from the PDC lineage commitment is regulated on the level of transcription factors reflected by down-regulation of E2-2 and up-regulation of ID2, PU.1, and BATF3. Thus, CCR9− PDCs are immediate PDC precursors that can be reprogrammed to differentiate into CDC-like cells with higher antigen-presenting and cytokine-producing capacity under the influence of the local tissue microenvironment.