title: The transcription factor Zeb2 regulates development of conventional and plasmacytoid DCs by repressing Id2.
abstract: Plasmacytoid dendritic cells (DCs [pDCs]) develop from pre-pDCs, whereas two lineages of conventional DCs (cDCs; cDC1s and cDC2s) develop from lineage-committed pre-cDCs. Several transcription factors (TFs) have been implicated in regulating the development of pDCs (E2-2 and Id2) and cDC1s (Irf8, Id2, and Batf3); however, those required for the early commitment of pre-cDCs toward the cDC2 lineage are unknown. Here, we identify the TF zinc finger E box-binding homeobox 2 (Zeb2) to play a crucial role in regulating DC development. Zeb2 was expressed from the pre-pDC and pre-cDC stage onward and highly expressed in mature pDCs and cDC2s. Mice conditionally lacking Zeb2 in CD11c(+) cells had a cell-intrinsic reduction in pDCs and cDC2s, coupled with an increase in cDC1s. Conversely, mice in which CD11c(+) cells overexpressed Zeb2 displayed a reduction in cDC1s. This was accompanied by altered expression of Id2, which was up-regulated in cDC2s and pDCs from conditional knockout mice. Zeb2 chromatin immunoprecipitation analysis revealed Id2 to be a direct target of Zeb2. Thus, we conclude that Zeb2 regulates commitment to both the cDC2 and pDC lineages through repression of Id2.
authors.affiliation: Laboratory of Immunoregulation and Mucosal Immunology, Inflammation Research Center, Vlaams Instituut voor Biotechnologie, 9052 Ghent, Belgium Department of Respiratory Medicine, Ghent University, 9000 Ghent, Belgium Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium.
authors.forename: Charlotte L
authors.initials: CL
authors.lastname: Scott
authors.affiliation: Unit of Molecular and Cellular Oncology, Inflammation Research Center, Vlaams Instituut voor Biotechnologie, 9052 Ghent, Belgium Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium.
authors.forename: Bieke
authors.initials: B
authors.lastname: Soen
authors.affiliation: Data Mining and Modeling for Biomedicine, Inflammation Research Center, Vlaams Instituut voor Biotechnologie, 9052 Ghent, Belgium Department of Respiratory Medicine, Ghent University, 9000 Ghent, Belgium.
authors.forename: Liesbet
authors.initials: L
authors.lastname: Martens
authors.affiliation: Unit of Molecular and Cellular Oncology, Inflammation Research Center, Vlaams Instituut voor Biotechnologie, 9052 Ghent, Belgium Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Skrypek
authors.affiliation: Data Mining and Modeling for Biomedicine, Inflammation Research Center, Vlaams Instituut voor Biotechnologie, 9052 Ghent, Belgium Department of Respiratory Medicine, Ghent University, 9000 Ghent, Belgium.
authors.forename: Wouter
authors.initials: W
authors.lastname: Saelens
authors.affiliation: Unit of Molecular and Cellular Oncology, Inflammation Research Center, Vlaams Instituut voor Biotechnologie, 9052 Ghent, Belgium Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium.
authors.forename: Joachim
authors.initials: J
authors.lastname: Taminau
authors.affiliation: Unit of Molecular and Cellular Oncology, Inflammation Research Center, Vlaams Instituut voor Biotechnologie, 9052 Ghent, Belgium Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium.
authors.forename: Gillian
authors.initials: G
authors.lastname: Blancke
authors.affiliation: Laboratory of Immunoregulation and Mucosal Immunology, Inflammation Research Center, Vlaams Instituut voor Biotechnologie, 9052 Ghent, Belgium Department of Respiratory Medicine, Ghent University, 9000 Ghent, Belgium.
authors.forename: Gert
authors.initials: G
authors.lastname: Van Isterdael
authors.affiliation: Laboratory of Molecular Biology (Celgen), Department of Development and Regeneration, Katholieke Universiteit Leuven, 3000 Leuven, Belgium Department of Cell Biology, Erasmus University Medical Center, 3015 GE Rotterdam, Netherlands.
authors.forename: Danny
authors.initials: D
authors.lastname: Huylebroeck
authors.affiliation: Mammalian Functional Genetics Laboratory, Division of Blood Cancers, Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria 3800, Australia.
authors.forename: Jody
authors.initials: J
authors.lastname: Haigh
authors.affiliation: Data Mining and Modeling for Biomedicine, Inflammation Research Center, Vlaams Instituut voor Biotechnologie, 9052 Ghent, Belgium Department of Respiratory Medicine, Ghent University, 9000 Ghent, Belgium.
authors.forename: Yvan
authors.initials: Y
authors.lastname: Saeys
authors.affiliation: Laboratory of Immunoregulation and Mucosal Immunology, Inflammation Research Center, Vlaams Instituut voor Biotechnologie, 9052 Ghent, Belgium Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium.
authors.forename: Martin
authors.initials: M
authors.lastname: Guilliams
authors.affiliation: Laboratory of Immunoregulation and Mucosal Immunology, Inflammation Research Center, Vlaams Instituut voor Biotechnologie, 9052 Ghent, Belgium Department of Respiratory Medicine, Ghent University, 9000 Ghent, Belgium Department of Pulmonary Medicine, Erasmus University Medical Center, 3015 GE Rotterdam, Netherlands bart.lambrecht@irc.vib-ugent.be Geert.Berx@irc.vib-ugent.be.
authors.forename: Bart N
authors.initials: BN
authors.lastname: Lambrecht
authors.affiliation: Unit of Molecular and Cellular Oncology, Inflammation Research Center, Vlaams Instituut voor Biotechnologie, 9052 Ghent, Belgium Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium bart.lambrecht@irc.vib-ugent.be Geert.Berx@irc.vib-ugent.be.
authors.forename: Geert
authors.initials: G
authors.lastname: Berx
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology*; D051797:Inhibitor of Differentiation Protein 2 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology*; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology*; D000074165:Zinc Finger E-box Binding Homeobox 2
chemical_list: D018398:Homeodomain Proteins; C497452:Idb2 protein, mouse; D051797:Inhibitor of Differentiation Protein 2; D012097:Repressor Proteins; C120602:ZEB2 protein, mouse; D000074165:Zinc Finger E-box Binding Homeobox 2