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Interferon priming is essential for human CD34+ cell-derived plasmacytoid dendritic cell maturation and function

Author

Listed:
  • A. Laustsen

    (Aarhus University)

  • R. O. Bak

    (Aarhus University
    Aarhus University
    Stanford University)

  • C. Krapp

    (Aarhus University)

  • L. Kjær

    (Aarhus University)

  • J. H. Egedahl

    (Aarhus University
    University of California
    The J. David Gladstone Institutes)

  • C. C. Petersen

    (Aarhus University)

  • S. Pillai

    (Blood Systems Research Institute)

  • H. Q. Tang

    (Aarhus University Hospital Skejby)

  • N. Uldbjerg

    (Aarhus University Hospital Skejby)

  • M. Porteus

    (Stanford University)

  • N. R. Roan

    (University of California
    The J. David Gladstone Institutes)

  • M. Nyegaard

    (Aarhus University)

  • P. W. Denton

    (Aarhus University Hospital Skejby
    Aarhus University Hospital Skejby)

  • M. R. Jakobsen

    (Aarhus University)

Abstract

Plasmacytoid dendritic cells (pDC) are essential for immune competence. Here we show that pDC precursor differentiated from human CD34+ hematopoietic stem and progenitor cells (HSPC) has low surface expression of pDC markers, and has limited induction of type I interferon (IFN) and IL-6 upon TLR7 and TLR9 agonists treatment; by contrast, cGAS or RIG-I agonists-mediated activation is not altered. Importantly, after priming with type I and II IFN, these precursor pDCs attain a phenotype and functional activity similar to that of peripheral blood-derived pDCs. Data from CRISPR/Cas9-mediated genome editing of HSPCs further show that HSPC-pDCs with genetic modifications can be obtained, and that expression of the IFN-α receptor is essential for the optimal function, but dispensable for the differentiation, of HSPC-pDC percursor. Our results thus demonstrate the biological effects of IFNs for regulating pDC function, and provide the means of generating of gene-modified human pDCs.

Suggested Citation

  • A. Laustsen & R. O. Bak & C. Krapp & L. Kjær & J. H. Egedahl & C. C. Petersen & S. Pillai & H. Q. Tang & N. Uldbjerg & M. Porteus & N. R. Roan & M. Nyegaard & P. W. Denton & M. R. Jakobsen, 2018. "Interferon priming is essential for human CD34+ cell-derived plasmacytoid dendritic cell maturation and function," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05816-y
    DOI: 10.1038/s41467-018-05816-y
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    Cited by:

    1. Konstantin Lutz & Andrea Musumeci & Christopher Sie & Ezgi Dursun & Elena Winheim & Johannes Bagnoli & Christoph Ziegenhain & Lisa Rausch & Volker Bergen & Malte D. Luecken & Robert A. J. Oostendorp &, 2022. "Ly6D+Siglec-H+ precursors contribute to conventional dendritic cells via a Zbtb46+Ly6D+ intermediary stage," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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