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

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-? 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.

SUBMITTER: Laustsen A

PROVIDER: S-EPMC6117296 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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

Laustsen A A Bak R O RO Krapp C C Kjær L L Egedahl J H JH Petersen C C CC Pillai S S Tang H Q HQ Uldbjerg N N Porteus M M Roan N R NR Nyegaard M M Nyegaard M M Denton P W PW Jakobsen M R MR

Nature communications 20180830 1

Plasmacytoid dendritic cells (pDC) are essential for immune competence. Here we show that pDC precursor differentiated from human CD34<sup>+</sup> 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 ...[more]

PMID: 30166549

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Dataset Information

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

Publications

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

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