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Blood, 1 January 2008, Vol. 111, No. 1, pp. 150-159.
Prepublished online as a Blood First Edition Paper on October 4, 2007; DOI 10.1182/blood-2007-05-089292.
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Submitted May 8, 2007
Accepted September 25, 2007
M-CSF: a novel plasmacytoid and conventional dendritic cell poietin
Ben Fancke, Mark Suter, Hubertus Hochrein, and Meredith O'Keeffe*
Research Department, Bavarian Nordic GmbH, Munich, Germany
Department of Veterinary Science, University of Zurich, Zurich, Switzerland
* Corresponding author; email: meredith.okeeffe{at}bavarian-nordic.com.
The critical importance of plasmacytoid dendritic cells (pDC) 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 a Flt-3 ligand (FL) culture system of bone marrow cells has led to the simple generation of large numbers of pDC that resemble their in vivo steady state counterparts. The FL system has allowed unforeseen insight into the biology of pDC 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 IFN- production in response to CpG-containing oligonucleotides, a feature of pDC, develop within M-CSF-generated bone marrow cultures. Analysis of this phenomenon revealed that M-CSF is able to drive pDC as well as cDC from BM precursor cells in vitro. Furthermore, application of M-CSF to mice was able to drive pDC and cDC development in vivo. Importantly, employing mice deficient in FL indicated that the M-CSF driven generation of pDC and cDC in vitro and in vivo was independent of endogenous FL.
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