M-CSF: a novel plasmacytoid and conventional dendritic cell poietin.
The critical importance of plasmacytoid dendritic cells (pDCs) in viral infection, autoimmunity, and tolerance has focused major attention on these cells that are rare in blood and immune organs of humans and mice. The recent development of an Flt-3 ligand (FL) culture system of bone marrow cells has led to the simple generation of large numbers of pDCs that resemble their in vivo steady-state counterparts. The FL system has allowed unforeseen insight into the biology of pDCs, and it is assumed that FL is the crucial growth factor for these cells. Surprisingly we have found that a cell type with high capacity for interferon-alpha (IFN-alpha) production in response to CpG-containing oligonucleotides, a feature of pDCs, develop within macrophage-colony-stimulating factor (M-CSF)-generated bone marrow cultures. Analysis of this phenomenon revealed that M-CSF is able to drive pDCs as well as conventional DCs (cDCs) from BM precursor cells in vitro. Furthermore, application of M-CSF to mice was able to drive pDCs and cDCs development in vivo. It is noteworthy that using mice deficient in FL indicated that the M-CSF-driven generation of pDCs and cDCs in vitro and in vivo was independent of endogenous FL.
Fancke
Ben
B
Research Department, Bavarian Nordic GmbH, Martinsried, Germany.
Suter
Mark
M
Hochrein
Hubertus
H
O'Keeffe
Meredith
M
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D016466:CHO Cells; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D003713:Dendritic Cells / Q000166:cytology* / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006410:Hematopoiesis / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D008024:Ligands; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism* / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023461:Myeloid Progenitor Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism; D051199:Toll-Like Receptor 7 / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000378:metabolism
C408982:CPG-oligonucleotide; D008024:Ligands; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009838:Oligodeoxyribonucleotides; C477038:Tlr7 protein, mouse; C495370:Tlr9 protein, mouse; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; C084881:flt3 ligand protein; D049452:Green Fluorescent Proteins; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma; D016186:Receptor, Macrophage Colony-Stimulating Factor