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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD34 / metabolism*
  • CRISPR-Cas Systems / genetics
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology
  • Cells, Cultured
  • DEAD Box Protein 58 / metabolism
  • Dendritic Cells / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Gene Editing
  • Humans
  • Interferon Type I / metabolism
  • Interleukin-6 / metabolism
  • Nucleotidyltransferases / metabolism
  • Polymerase Chain Reaction
  • Receptor, Interferon alpha-beta / genetics
  • Receptor, Interferon alpha-beta / metabolism
  • Toll-Like Receptor 7 / agonists
  • Toll-Like Receptor 9 / agonists

Substances

  • Antigens, CD34
  • Interferon Type I
  • Interleukin-6
  • TLR7 protein, human
  • TLR9 protein, human
  • Toll-Like Receptor 7
  • Toll-Like Receptor 9
  • Receptor, Interferon alpha-beta
  • Nucleotidyltransferases
  • cGAS protein, human
  • DDX58 protein, human
  • DEAD Box Protein 58