title: IRF8 Transcription Factor Controls Survival and Function of Terminally Differentiated Conventional and Plasmacytoid Dendritic Cells, Respectively.
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 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.
authors.affiliation: Lab of Immunoregulation, VIB Inflammation Research Center, Ghent University, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium.
authors.forename: Dorine
authors.initials: D
authors.lastname: Sichien
authors.affiliation: Lab of Immunoregulation, VIB Inflammation Research Center, Ghent University, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium.
authors.forename: Charlotte L
authors.initials: CL
authors.lastname: Scott
authors.affiliation: Department of Respiratory Medicine, University Hospital Ghent, 9000 Ghent, Belgium; Data Mining and Modelling for Biomedicine Group, VIB Inflammation Research Center, Ghent University, 9052 Ghent, Belgium.
authors.forename: Liesbet
authors.initials: L
authors.lastname: Martens
authors.affiliation: Lab of Immunoregulation, VIB Inflammation Research Center, Ghent University, 9052 Ghent, Belgium; Department of Respiratory Medicine, University Hospital Ghent, 9000 Ghent, Belgium.
authors.forename: Matthias
authors.initials: M
authors.lastname: Vanderkerken
authors.affiliation: Lab of Immunoregulation, VIB Inflammation Research Center, Ghent University, 9052 Ghent, Belgium; Data Mining and Modelling for Biomedicine Group, VIB Inflammation Research Center, Ghent University, 9052 Ghent, Belgium; Department of Information Technology, iMinds, Ghent University, Ghent, Belgium.
authors.forename: Sofie
authors.initials: S
authors.lastname: Van Gassen
authors.affiliation: Lab of Immunoregulation, VIB Inflammation Research Center, Ghent University, 9052 Ghent, Belgium; Department of Respiratory Medicine, University Hospital Ghent, 9000 Ghent, Belgium.
authors.forename: Maud
authors.initials: M
authors.lastname: Plantinga
authors.affiliation: Section of Immunology and Vaccinology, Danish Technical University Veterinary Institute, 1870 Copenhagen, Denmark.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Joeris
authors.affiliation: Lab of Immunoregulation, VIB Inflammation Research Center, Ghent University, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium.
authors.forename: Sofie
authors.initials: S
authors.lastname: De Prijck
authors.affiliation: Lab of Immunoregulation, VIB Inflammation Research Center, Ghent University, 9052 Ghent, Belgium; Department of Medical Genetics, University Hospital Ghent, 9000 Ghent, Belgium.
authors.forename: Leen
authors.initials: L
authors.lastname: Vanhoutte
authors.affiliation: Lab of Immunoregulation, VIB Inflammation Research Center, Ghent University, 9052 Ghent, Belgium; Department of Respiratory Medicine, University Hospital Ghent, 9000 Ghent, Belgium.
authors.forename: Manon
authors.initials: M
authors.lastname: Vanheerswynghels
authors.affiliation: Lab of Immunoregulation, VIB Inflammation Research Center, Ghent University, 9052 Ghent, Belgium; Department of Respiratory Medicine, University Hospital Ghent, 9000 Ghent, Belgium.
authors.forename: Gert
authors.initials: G
authors.lastname: Van Isterdael
authors.affiliation: Lab of Immunoregulation, VIB Inflammation Research Center, Ghent University, 9052 Ghent, Belgium; Department of Respiratory Medicine, University Hospital Ghent, 9000 Ghent, Belgium.
authors.forename: Wendy
authors.initials: W
authors.lastname: Toussaint
authors.affiliation: Lab of Immunoregulation, VIB Inflammation Research Center, Ghent University, 9052 Ghent, Belgium; Department of Respiratory Medicine, University Hospital Ghent, 9000 Ghent, Belgium.
authors.forename: Filipe Branco
authors.initials: FB
authors.lastname: Madeira
authors.affiliation: Lab of Immunoregulation, VIB Inflammation Research Center, Ghent University, 9052 Ghent, Belgium; Department of Respiratory Medicine, University Hospital Ghent, 9000 Ghent, Belgium.
authors.forename: Karl
authors.initials: K
authors.lastname: Vergote
authors.affiliation: Section of Immunology and Vaccinology, Danish Technical University Veterinary Institute, 1870 Copenhagen, Denmark; Department of Experimental Medical Science, Immunology Section, Lund University, 221 00 Lund, Sweden.
authors.forename: William W
authors.initials: WW
authors.lastname: Agace
authors.affiliation: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany.
authors.forename: Björn E
authors.initials: BE
authors.lastname: Clausen
authors.affiliation: Lab of Immunoregulation, VIB Inflammation Research Center, Ghent University, 9052 Ghent, Belgium; Department of Respiratory Medicine, University Hospital Ghent, 9000 Ghent, Belgium.
authors.forename: Hamida
authors.initials: H
authors.lastname: Hammad
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, UNIV UM2, Aix-Marseille Université, Parc Scientifique et Technologique de Luminy, 13288 Marseille, France; INSERM, U1104, 13288 Marseille, France; CNRS, UMR7280, 13288 Marseille, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Dalod
authors.affiliation: Lab of Immunoregulation, VIB Inflammation Research Center, Ghent University, 9052 Ghent, Belgium; Department of Respiratory Medicine, University Hospital Ghent, 9000 Ghent, Belgium; Data Mining and Modelling for Biomedicine Group, VIB Inflammation Research Center, Ghent University, 9052 Ghent, Belgium.
authors.forename: Yvan
authors.initials: Y
authors.lastname: Saeys
authors.affiliation: Lab of Immunoregulation, VIB Inflammation Research Center, Ghent University, 9052 Ghent, Belgium; Department of Respiratory Medicine, University Hospital Ghent, 9000 Ghent, Belgium; Department of Pulmonary Medicine, Erasmus MC, University Medical Center, Rotterdam, 3015 the Netherlands. Electronic address: bart.lambrecht@irc.vib-ugent.be.
authors.forename: Bart N
authors.initials: BN
authors.lastname: Lambrecht
authors.affiliation: Lab of Immunoregulation, VIB Inflammation Research Center, Ghent University, 9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium. Electronic address: martin.guilliams@irc.vib-ugent.be.
authors.forename: Martin
authors.initials: M
authors.lastname: Guilliams
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D003713:Dendritic Cells / Q000378:metabolism* / Q000502:physiology*; D050835:Interferon Regulatory Factors / Q000378:metabolism*; D007370:Interferon Type I / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000378:metabolism / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000502:physiology; D013601:T-Lymphocytes / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism*; D000099185:Interferon Regulatory Factor-8
chemical_list: D050835:Interferon Regulatory Factors; D007370:Interferon Type I; D014157:Transcription Factors; D000099185:Interferon Regulatory Factor-8
keywords: IRF4; IRF8; dendritic cell; development; lineage; monocyte; plasmacytoid dendritic cell; terminal selector; transcription factor