Institut for Biomedicin

Rasmus Bak

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

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

DOI

  • A Laustsen
  • Rasmus Bak
  • Christian Krapp
  • L Kjær
  • J H Egedahl, The J. David Gladstone Institutes, San Francisco, CA, 94158, USA.
  • ,
  • C C Petersen
  • S Pillai, University of California, San Francisco, Blood Systems Research Institute, 270 Masonic Avenue, San Francisco, 94118-4417, CA, USA.
  • ,
  • H Q Tang
  • N Uldbjerg
  • M Porteus, Department of Pediatrics, Stanford University, Stanford, California 94305, USA.
  • ,
  • N R Roan, The J. David Gladstone Institutes, San Francisco, CA, 94158, USA.
  • ,
  • M Nyegaard
  • P W Denton
  • ,
  • M R Jakobsen

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.

OriginalsprogEngelsk
Artikelnummer3525
TidsskriftNature Communications
Vol/bind9
Nummer1
Antal sider14
ISSN2041-1723
DOI
StatusUdgivet - 30 aug. 2018

Se relationer på Aarhus Universitet Citationsformater

ID: 132185583