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Nat Commun. 2018 Aug 30;9(1):3525. doi: 10.1038/s41467-018-05816-y.

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

Author information

1
Department of Biomedicine, Aarhus University, Wilhelm Meyers Alle 4, 8000, Aarhus C, Denmark.
2
Aarhus Institute of Advanced Studies (AIAS), Aarhus University, Høegh-Guldbergs Gade 6B, 8000, Aarhus C, Denmark.
3
Department of Pediatrics, Stanford University, Stanford, CA, 94305, USA.
4
Department of Urology, University of California, San Francisco, CA, 94158, USA.
5
The J. David Gladstone Institutes, San Francisco, CA, 94158, USA.
6
University of California, San Francisco, Blood Systems Research Institute, 270 Masonic Avenue, San Francisco, 94118-4417, CA, USA.
7
Department of Obstetrics and Gynaecology, Aarhus University Hospital Skejby, Aarhus, 8200, Denmark.
8
Department of Infectious Diseases, Aarhus University Hospital Skejby, Aarhus, 8200, Denmark.
9
Department of Clinical Medicine, Aarhus University Hospital Skejby, Aarhus, 8200, Denmark.
10
Department of Biomedicine, Aarhus University, Wilhelm Meyers Alle 4, 8000, Aarhus C, Denmark. mrj@biomed.au.dk.

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.

PMID:
30166549
PMCID:
PMC6117296
DOI:
10.1038/s41467-018-05816-y
[Indexed for MEDLINE]
Free PMC Article

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