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

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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.

Original languageEnglish
Article number3525
JournalNature Communications
Volume9
Issue1
Number of pages14
ISSN2041-1723
DOIs
Publication statusPublished - 30 Aug 2018

    Research areas

  • ADJUVANT ACTIVITY, BONE-MARROW, DIABETES-MELLITUS, FLT3 LIGAND, HEMATOPOIETIC STEM-CELLS, I-INTERFERON, IFN-ALPHA, MAMMALIAN-CELLS, PROGENITOR CELLS, SYNTHETIC SIRNA

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