The Notch ligand delta-1 is a hematopoietic development cofactor for plasmacytoid dendritic cells

DOI PDF 被引用文献3件
  • Aurélie Olivier
    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.
  • Evelyne Lauret
    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.
  • Patrick Gonin
    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.
  • 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.

抄録

<jats:title>Abstract</jats:title><jats:p>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-Tα mRNAs, and secreting CpG-induced IFN-α. Delta-1 augmented the numbers of BDCA-2+ cells produced without affecting their proliferation, and the effect was blocked by γ-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.</jats:p>

収録刊行物

  • Blood

    Blood 107 (7), 2694-2701, 2006-04-01

    American Society of Hematology

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