title: 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.
authors.affiliation: II Medical Department, Klinikum rechts der Isar, Technical University Munich, Trogerstrasse 32/1.04, Munich, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schlitzer
authors.forename: Jakob
authors.initials: J
authors.lastname: Loschko
authors.forename: Katrin
authors.initials: K
authors.lastname: Mair
authors.forename: Roger
authors.initials: R
authors.lastname: Vogelmann
authors.forename: Lynette
authors.initials: L
authors.lastname: Henkel
authors.forename: Henrik
authors.initials: H
authors.lastname: Einwächter
authors.forename: Matthias
authors.initials: M
authors.lastname: Schiemann
authors.forename: Jan-Hendrik
authors.initials: JH
authors.lastname: Niess
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Reindl
authors.forename: Anne
authors.initials: A
authors.lastname: Krug
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000502:physiology; D039481:CD11b Antigen / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D054388:Receptors, CCR / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*
chemical_list: C119309:CC chemokine receptor 9; D039481:CD11b Antigen; D054388:Receptors, CCR; D016178:Granulocyte-Macrophage Colony-Stimulating Factor