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

Abstract:

: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 II(low) 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 II(high) 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.

journal_name

Blood

journal_title

Blood

authors

Schlitzer A,Loschko J,Mair K,Vogelmann R,Henkel L,Einwächter H,Schiemann M,Niess JH,Reindl W,Krug A

doi

10.1182/blood-2010-12-326678

subject

Has Abstract

pub_date

2011-06-16 00:00:00

pages

6562-70

issue

24

eissn

0006-4971

issn

1528-0020

pii

blood-2010-12-326678

journal_volume

117

pub_type

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