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

By M. Gilliet, A. Boonstra, C. Paturel, S. Antonenko, Xiu-ling Xu, G. Trinchieri, A. O’Garra, Yong‐jun Liu. Journal of Experimental Medicine, 2002

603 citations recorded by the source corpus.

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.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/749c410625d55f40fe5e25db67f16087b05ef1da

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In Immunology

1. Shizuo Akira
2. R. Medzhitov
3. Jonathan C. Kagan
4. Yong‐jun Liu
5. G. Barton
6. R. Steinman
7. Taro Kawai
8. H. Hemmi

Citations in the corpus

• Flexibility of Mouse Classical and Plasmacytoid-derived Dendritic Cells in Directing T Helper Type 1 and 2 Cell Development (2003, methodology): “Additionally, plasmacytoid pDCs expressing CD11c CD11b B220 were purified by flow cytometry after culture of bone marrow cells in the presence of Flt3 ligand (43).”
• Cutting Edge: Generation of Splenic CD8+ and CD8− Dendritic Cell Equivalents in Fms-Like Tyrosine Kinase 3 Ligand Bone Marrow Cultures1 (2005, positive): “1A), as others have noted previously (8, 9, 16).”
• Identification of clonogenic common Flt3+M-CSFR+ plasmacytoid and conventional dendritic cell progenitors in mouse bone marrow (2007, background): “Flt3 ligand (Flt3L) is sufficient to induce the differentiation of both pDCs and cDCs from progenitors in vitro”
• Dendritic cells: translating innate to adaptive immunity. (2006, background): “In other words, because more NF-κB is available, TLRs and other transducers of maturation may lead to stronger and more rapid responses in DCs.”
• Toll-like receptors on hematopoietic progenitor cells stimulate innate immune system replenishment. (2006, background): “GM-CSF and TNFα were of particular interest because they can promote the production of DCs from bone marrow in vitro (Gilliet et al., 2002) and TNFα can suppress B-lymphopoiesis (Sedger et al., 2002).”
• Development of plasmacytoid and conventional dendritic cell subtypes from single precursor cells derived in vitro and in vivo (2007, background): “, so culture of bone marrow precursor cells with Flt3”
• Essential Role of Lung Plasmacytoid Dendritic Cells in Preventing Asthmatic Reactions to Harmless Inhaled Antigen (2004, methodology): “Alternative explanations could be that immature lung pDCs are important for generating T reg cells after exposure of harmless antigen, as proposed in vitro by others (27, 29, 39, 43) and also shown indirectly ex vivo here (Fig.”
• Intracellular localization of Toll-like receptor 9 prevents recognition of self DNA but facilitates access to viral DNA (2006, background): “Flt3L-derived DC cultures contain both plasmacytoid DCs and conventional DC”
• Plasmacytoid Dendritic Cells: Recent Progress and Open Questions (2011, background): “Subsequently, the murine counterparts of human pDCs were identified (20–22), and in vitro derivation of pDCs from human and murine hematopoietic progenitors was established (23, 24).”