The development of murine plasmacytoid dendritic cell precursors is differentially regulated by FLT3-ligand and granulocyte/macrophage colony-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-alpha, 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-alpha 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.
Gilliet
Michel
M
DNAX Research Institute, Palo Alto, CA 94304, USA.
Boonstra
Andre
A
Paturel
Carine
C
Antonenko
Svetlana
S
Xu
Xiu-Ling
XL
Trinchieri
Giorgio
G
O'Garra
Anne
A
Liu
Yong-Jun
YJ
D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006410:Hematopoiesis; D006801:Humans; D007700:Kinetics; D016177:Macrophage-1 Antigen / Q000032:analysis; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D013045:Species Specificity; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000943:Antigens, Differentiation; D016177:Macrophage-1 Antigen; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha; C084881:flt3 ligand protein; D016178:Granulocyte-Macrophage Colony-Stimulating Factor