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

Research output: Contribution to journalJournal article – Annual report year: 2016Researchpeer-review

  • Author: Sichien, Dorine

    Ghent University, Belgium

  • Author: Scott, Charlotte L.

    Ghent University, Belgium

  • Author: Martens, Liesbet

    Ghent University, Belgium

  • Author: Vanderkerken, Matthias

    Ghent University, Belgium

  • Author: Van Gassen, Sofie

  • Author: Plantinga, Maud

    Ghent University, Belgium

  • Author: Joeris, Thorsten

    Section for Immunology and Vaccinology, National Veterinary Institute, Technical University of Denmark, Kemitorvet, 2800, Kgs. Lyngby, Denmark

  • Author: De Prijck, Sofie

    Ghent University, Belgium

  • Author: Vanhoutte, Leen

    Ghent University, Belgium

  • Author: Vanheerswynghels, Manon

    Ghent University, Belgium

  • Author: Van Isterdael, Gert

    Ghent University, Belgium

  • Author: Toussaint, Wendy

    Ghent University, Belgium

  • Author: Madeira, Filipe Branco

    Ghent University, Belgium

  • Author: Vergote, Karl

    Ghent University, Belgium

  • Author: Agace, William Winston

    Section for Immunology and Vaccinology, National Veterinary Institute, Technical University of Denmark, Kemitorvet, 2800, Kgs. Lyngby, Denmark

  • Author: Clausen, Björn E.

    Johannes Gutenberg University Mainz, Germany

  • Author: Hammad, Hamida

    Ghent University, Belgium

  • Author: Dalod, Marc

    CNRS, France

  • Author: Saeys, Yvan

    Ghent University, Belgium

  • Author: Lambrecht, Bart N.

    Ghent University, Belgium

  • Author: Guilliams, Martin

    Ghent University, Belgium

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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 Irf8(fl/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.
Original languageEnglish
JournalImmunity
Volume45
Issue number3
Pages (from-to)626-640
Number of pages15
ISSN1074-7613
DOIs
Publication statusPublished - 2016
CitationsWeb of Science® Times Cited: No match on DOI

    Research areas

  • IRF4, IRF8, dendritic cell, development, lineage, monocyte, plasmacytoid dendritic cell, terminal selector, transcription factor
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