Journal
BLOOD
Volume 117, Issue 24, Pages 6562-6570Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2010-12-326678
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Funding
- German Research Foundation [KR2199/1-4, KR2199/3-1, SFB 455, SFB 571, GRK 1482, Ni575/6-2, Ni575/7-1]
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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(+) CD8 alpha(-) 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 downregulation 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. (Blood. 2011; 117(24):6562-6570)
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