scholarly journals The Development of Murine Plasmacytoid Dendritic Cell Precursors Is Differentially Regulated by FLT3-ligand and Granulocyte/Macrophage Colony-Stimulating Factor

2002 ◽  
Vol 195 (7) ◽  
pp. 953-958 ◽  
Author(s):  
Michel Gilliet ◽  
Andre Boonstra ◽  
Carine Paturel ◽  
Svetlana Antonenko ◽  
Xiu-Ling Xu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Herpes Simplex ◽  
Cpg Odn ◽  
Colony Stimulating Factor ◽  
Flt3 Ligand ◽  
Large Numbers ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Simplex Virus ◽  
Stimulating Factor

Plasmacytoid predendritic cells or type 1 interferon (IFN)-producing cells (IPCs) have recently been identified in mice. Although culture systems giving rise to different murine dendritic cell subsets have been established, the developmental regulation of murine plasmacytoid IPCs and the culture conditions leading to their generation remain unknown. Here we show that large numbers of over 40% pure CD11c+CD11b−B220+Gr-1+ IPCs can be generated from mouse bone marrow cultures with FLT3-ligand. By contrast GM-CSF or TNF-α, which promote the generation of CD11c+CD11b+B220− myeloid DCs, block completely the development of IPCs. IPCs generated display similar features to human IPCs, such as the plasmacytoid morphology, the ability to produce large amounts of IFN-α in responses to herpes simplex virus, and the capacity to respond to ligands for Toll-like receptor 9 (TLR-9; CpG ODN 1668), but not to ligands for TLR-4 (lipopolysaccharide [LPS]). Unlike human IPCs which produce little IL-12p70, mouse IPCs produce IL-12p70 in response to CpG ODN 1668 and herpes simplex virus. This study demonstrates that the development of murine CD11c+CD11b−B220+Gr-1+ IPCs and CD11c+CD11b+B220− myeloid DCs is differentially regulated by FLT3-ligand and granulocyte/macrophage colony-stimulating factor. Human IPCs and mouse IPCs display different ability to produce IL-12p70. Large numbers of mouse IPCs can now be obtained from total bone marrow culture.

FLT3 ligand can substitute for macrophage colony-stimulating factor in support of osteoclast differentiation and function

Blood ◽  
2001 ◽  
Vol 98 (9) ◽  
pp. 2707-2713 ◽  
Author(s):  
Jeny Maree Lean ◽  
Karen Fuller ◽  
Timothy John Chambers
Keyword(s):  
Bone Marrow ◽  
Bone Resorption ◽  
Bone Marrow Cells ◽  
Osteoclast Differentiation ◽  
Colony Stimulating Factor ◽  
Flt3 Ligand ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Marrow Cells

Abstract Although bone resorption and osteoclast numbers are reduced in osteopetrotic (op/op) mice, osteoclasts are nevertheless present and functional, despite the absence of macrophage colony-stimulating factor (M-CSF). This suggests that alternative factors can partly compensate for the crucial actions of M-CSF in osteoclast induction. It was found that when nonadherent bone marrow cells were incubated in RANKL with Flt3 ligand (FL) without exogenous M-CSF, tartrate-resistance acid phosphatase (TRAP)–positive cells were formed, and bone resorption occurred. Without FL, only macrophagelike TRAP-negative cells were present. Granulocyte-macrophage CSF, stem cell factor, interleukin-3, and vascular endothelial growth factor could not similarly replace the need for M-CSF. TRAP-positive cell induction in FL was not due to synergy with M-CSF produced by the bone marrow cells themselves because FL also enabled their formation from the hemopoietic cells of op/op mice, which lack any M-CSF. FL appeared to substitute for M-CSF by supporting the differentiation of adherent cells that express mRNA for RANK and responsiveness to RANKL. To determine whether FL can account for the compensation for M-CSF deficiency that occurs in vivo, FL signaling was blockaded in op/op mice by the injection of soluble recombinant Flt3. It was found that the soluble receptor induced a substantial decrease in osteoclast number, strongly suggesting that FL is responsible for the partial compensation for M-CSF deficiency that occurs in these mice.

Isolation and characterization of plasmacytoid dendritic cells from Flt3 ligand and granulocyte-macrophage colony-stimulating factor–treated mice

Blood ◽  
2001 ◽  
Vol 98 (13) ◽  
pp. 3520-3526 ◽  
Author(s):  
Pia Björck
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Colony Stimulating Factor ◽  
Flt3 Ligand ◽  
Isolation And Characterization ◽  
Macrophage Colony Stimulating Factor ◽  
Plasmacytoid Dcs ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract Interferon α/β plays an important role in the first-line defense against viral infections and can modulate cytokine responses by T-helper cells. Type 1 interferons (IFNs) are clinically important in infectious diseases and in the treatment of leukemia and lymphomas. Many different cell types have the capacity to produce IFN-α after encounter with virus and bacteria. The major, natural type 1 IFN–producing cell in humans was recently described as the plasmacytoid T cell, or pDC2, and it can differentiate into dendritic cells (DCs) on culture. This study describes the murine natural IFN-α–producing cell, or pDC2, that shares morphologic features with its human counterpart but has some distinct phenotypical characteristics. Murine plasmacytoid DCs can be differentially isolated based on their expression of CD11c, B220 (CD45R), and Thy1.2 (CD90). They lack expression of myeloid (eg, CD11b) antigens and CD8α, a marker used to isolate lymphoid DCs. Like human pDC2, murine plasmacytoid DCs exhibit their maximal type 1 IFN–producing capacity at a precursor stage; pDCs isolated from bone marrow responded to viral stimulation with higher IFN-α production than cells of the same phenotype isolated from spleen. Mobilization of mice with Flt3 ligand (Flt3L) or Flt3L and granulocyte-macrophage colony-stimulating factor, hematopoietic factors that specifically enhance DC growth, resulted in strikingly increased numbers of pDC in bone marrow and spleen. The isolation of this novel murine DC subset may serve as a useful tool in the study of viral immunobiology and for the design of treatments for murine malignancies.

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