IRF8 Transcription Factor Controls Survival and Function of Terminally Differentiated Conventional and Plasmacytoid Dendritic Cells, Respectively

Research output: Contribution to journalArticle

Abstract

Interferon regulatory factor-8 (IRF8) has been proposed to be essential for development of monocytes, plasmacytoid dendritic cells (pDCs) and type 1 conventional dendritic cells (cDC1s) and remains highly expressed in differentiated DCs. Transcription factors that are required to maintain the identity of terminally differentiated cells are designated “terminal selectors.” Using BM chimeras, conditional Irf8fl/fl mice and various promotors to target Cre recombinase to different stages of monocyte and DC development, we have identified IRF8 as a terminal selector of the cDC1 lineage controlling survival. In monocytes, IRF8 was necessary during early but not late development. Complete or late deletion of IRF8 had no effect on pDC development or survival but altered their phenotype and gene-expression profile leading to increased T cell stimulatory function but decreased type 1 interferon production. Thus, IRF8 differentially controls the survival and function of terminally differentiated monocytes, cDC1s, and pDCs.

Details

Authors
  • Dorine Sichien
  • Charlotte L. Scott
  • Liesbet Martens
  • Matthias Vanderkerken
  • Sofie Van Gassen
  • Maud Plantinga
  • Thorsten Joeris
  • Sofie De Prijck
  • Leen Vanhoutte
  • Manon Vanheerswynghels
  • Gert Van Isterdael
  • Wendy Toussaint
  • Filipe Branco Madeira
  • Karl Vergote
  • Björn E. Clausen
  • Hamida Hammad
  • Marc Dalod
  • Yvan Saeys
  • Bart N. Lambrecht
  • Martin Guilliams
Organisations
External organisations
  • Ghent University
  • Ghent University Hospital
  • Technical University of Denmark
  • University of Mainz
  • Erasmus University Medical Center
  • Aix-Marseille University
  • Centre d'Immunologie Marseille Luminy
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Immunology in the medical area

Keywords

  • dendritic cell, development, IRF4, IRF8, lineage, monocyte, plasmacytoid dendritic cell, terminal selector, transcription factor
Original languageEnglish
Pages (from-to)626-640
Number of pages15
JournalImmunity
Volume45
Issue number3
Publication statusPublished - 2016 Sep 20
Publication categoryResearch
Peer-reviewedYes