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

Nature Communications
A LaustsenM R Jakobsen

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.

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Citations

Jun 13, 2020·Frontiers in Cellular and Infection Microbiology·Renée M van der SluisMartin R Jakobsen
Nov 30, 2019·Nature Communications·Caleb R Perez, Michele De Palma
Apr 28, 2021·ELife·Marco JostJonathan S Weissman
Aug 8, 2021·Advanced Drug Delivery Reviews·Yingyue DingQuanyin Hu

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Methods Mentioned

BETA
density-gradient centrifugation
flow cytometry
RNA-seq
genetic modifications
Assay
ELISA
PCR
FCS

Software Mentioned

STAR
FlowJo
GraphPad
Partek
Partek Flow
TIDE ( Tracking Decomposition
GraphPad Prism
Partek Flow built

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