title: Tissue-specific differentiation of a circulating CCR9- pDC-like common dendritic cell precursor.
abstract: The ontogenic relationship between the common dendritic cell (DC) progenitor (CDP), the committed conventional DC precursor (pre-cDC), and cDC subpopulations in lymphoid and nonlymphoid tissues has been largely unraveled. In contrast, the sequential steps of plasmacytoid DC (pDC) development are less defined, and it is unknown at which developmental stage and location final commitment to the pDC lineage occurs. Here we show that CCR9(-) pDCs from murine BM which enter the circulation and peripheral tissues have a common DC precursor function in vivo in the steady state, in contrast to CCR9(+) pDCs which are terminally differentiated. On adoptive transfer, the fate of CCR9(-) pDC-like precursors is governed by the tissues they enter. In the BM and liver, most transferred CCR9(-) pDC-like precursors differentiate into CCR9(+) pDCs, whereas in peripheral lymphoid organs, lung, and intestine, they additionally give rise to cDCs. CCR9(-) pDC-like precursors which are distinct from pre-cDCs can be generated from the CDP. Thus, CCR9(-) pDC-like cells are novel CDP-derived circulating DC precursors with pDC and cDC potential. Their final differentiation into functionally distinct pDCs and cDCs depends on tissue-specific factors allowing adaptation to local requirements under homeostatic conditions.
authors.affiliation: II Medical Department, Klinikum Rechts der Isar, Technical University Munich, Ismaningerstrasse 22, Munich, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schlitzer
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Heiseke
authors.forename: Henrik
authors.initials: H
authors.lastname: Einwächter
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Reindl
authors.forename: Matthias
authors.initials: M
authors.lastname: Schiemann
authors.forename: Calin-Petru
authors.initials: CP
authors.lastname: Manta
authors.forename: Peter
authors.initials: P
authors.lastname: See
authors.forename: Jan-Hendrik
authors.initials: JH
authors.lastname: Niess
authors.forename: Tobias
authors.initials: T
authors.lastname: Suter
authors.forename: Florent
authors.initials: F
authors.lastname: Ginhoux
authors.forename: Anne B
authors.initials: AB
authors.lastname: Krug
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism / Q000502:physiology*; D005260:Female; D020869:Gene Expression Profiling; D008221:Lymphoid Tissue / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009092:Mucous Membrane / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D009928:Organ Specificity / Q000235:genetics; D054388:Receptors, CCR / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology*
chemical_list: C119309:CC chemokine receptor 9; D054388:Receptors, CCR