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Blood, 1 April 2006, Vol. 107, No. 7, pp. 2694-2701. Prepublished online as a Blood First Edition Paper on December 15, 2005; DOI 10.1182/blood-2005-03-0970. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: 2005-03-0970v1 107/7/2694    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Olivier, A. Articles by Galy, A. Search for Related Content PubMed PubMed Citation Articles by Olivier, A. Articles by Galy, A. Related Collections Hematopoiesis and Stem Cells Immunobiology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS The Notch ligand delta-1 is a hematopoietic development cofactor for plasmacytoid dendritic cells Aurélie Olivier, Evelyne Lauret, Patrick Gonin, and Anne Galy From Institut National de la Santé et de la Recherche Médicale (INSERM) U362, Villejuif, France; Université Paris-Sud 11, Villejuif, France; Institut Gustave Roussy, Villejuif, France; and Généthon, Evry, France. Plasmacytoid dendritic cells (pDCs) play an important role in innate and adaptive immunity, prompting interest in mechanisms controlling the production of this lineage of cells. Notch signaling via one of the Notch ligands, delta-like 1 (delta-1), influences the hematopoietic development of several lymphoid and myeloid lineages, but whether or not delta-1 affects the formation of pDCs is unknown and was tested here. Human CD34+ progenitor cells were cultured onto delta-1–expressing OP9 stroma in the presence of flt-3 ligand and IL-7, and this efficiently generated BDCA-2+ CD123+ CD4+ CD11c– cells with the characteristic morphology of pDCs, expressing toll-like receptor-9 (TLR9), pre-T mRNAs, and secreting CpG-induced IFN-. Delta-1 augmented the numbers of BDCA-2+ cells produced without affecting their proliferation, and the effect was blocked by -secretase inhibition. The development of pDCs was stroma-, delta-1–, and cytokine-dependent and could be induced from committed lymphoid progenitor cells, which responded to delta-1 by opposite changes in pDC- and B-cell production. Our results identify delta-1 as a novel factor enhancing pDC hematopoiesis and delineate a new role for Notch signaling in lymphopoiesis by showing its opposite effect on pDC and B lineage determination. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y.-C. Wang, X.-B. Hu, F. He, F. Feng, L. Wang, W. Li, P. Zhang, D. Li, Z.-S. Jia, Y.-M. Liang, et al. Lipopolysaccharide-induced Maturation of Bone Marrow-derived Dendritic Cells Is Regulated by Notch Signaling through the Up-regulation of CXCR4 J. Biol. Chem., June 5, 2009; 284(23): 15993 - 16003. [Abstract] [Full Text] [PDF] J. F. Hutton, T. Gargett, T. J. Sadlon, S. Bresatz, C. Y. Brown, H. Zola, M. F. Shannon, R. J. D'Andrea, and S. C. Barry Development of CD4+CD25+FoxP3+ regulatory T cells from cord blood hematopoietic progenitor cells J. Leukoc. Biol., March 1, 2009; 85(3): 445 - 451. [Abstract] [Full Text] [PDF] R. S. Welner, R. Pelayo, Y. Nagai, K. P. Garrett, T. R. Wuest, D. J. Carr, L. A. Borghesi, M. A. Farrar, and P. W. Kincade Lymphoid precursors are directed to produce dendritic cells as a result of TLR9 ligation during herpes infection Blood, November 1, 2008; 112(9): 3753 - 3761. [Abstract] [Full Text] [PDF] Y.-P. Li, S. 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Masurier Major Subsets of Human Dendritic Cells Are Efficiently Transduced by Self-Complementary Adeno-Associated Virus Vectors 1 and 2 J. Virol., May 15, 2007; 81(10): 5385 - 5394. [Abstract] [Full Text] [PDF] M. Hiratochi, H. Nagase, Y. Kuramochi, C.-S. Koh, T. Ohkawara, and K. Nakayama The Delta intracellular domain mediates TGF-{beta}/Activin signaling through binding to Smads and has an important bi-directional function in the Notch-Delta signaling pathway Nucleic Acids Res., February 16, 2007; 35(3): 912 - 922. [Abstract] [Full Text] [PDF] P. Cheng, Y. Nefedova, C. A. Corzo, and D. I. Gabrilovich Regulation of dendritic-cell differentiation by bone marrow stroma via different Notch ligands Blood, January 15, 2007; 109(2): 507 - 515. [Abstract] [Full Text] [PDF]

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