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

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

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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.

Original languageEnglish (US)
Article number3525
JournalNature communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Fingerprint

Dive into the research topics of 'Interferon priming is essential for human CD34+ cell-derived plasmacytoid dendritic cell maturation and function'. Together they form a unique fingerprint.

Cite this