title: Batf3 maintains autoactivation of Irf8 for commitment of a CD8α(+) conventional DC clonogenic progenitor.
abstract: The transcription factors Batf3 and IRF8 are required for the development of CD8α(+) conventional dendritic cells (cDCs), but the basis for their actions has remained unclear. Here we identified two progenitor cells positive for the transcription factor Zbtb46 that separately generated CD8α(+) cDCs and CD4(+) cDCs and arose directly from the common DC progenitor (CDP). Irf8 expression in CDPs required prior autoactivation of Irf8 that was dependent on the transcription factor PU.1. Specification of the clonogenic progenitor of CD8α(+) cDCs (the pre-CD8 DC) required IRF8 but not Batf3. However, after specification of pre-CD8 DCs, autoactivation of Irf8 became Batf3 dependent at a CD8α(+) cDC-specific enhancer with multiple transcription factor AP1-IRF composite elements (AICEs) within the Irf8 superenhancer. CDPs from Batf3(-/-) mice that were specified toward development into pre-CD8 DCs failed to complete their development into CD8α(+) cDCs due to decay of Irf8 autoactivation and diverted to the CD4(+) cDC lineage.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Gary E
authors.initials: GE
authors.lastname: Grajales-Reyes
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Arifumi
authors.initials: A
authors.lastname: Iwata
authors.affiliation: Department of Medicine A, Hematology and Oncology, University of Muenster, Muenster, Germany.
authors.forename: Jörn
authors.initials: J
authors.lastname: Albring
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Xiaodi
authors.initials: X
authors.lastname: Wu
authors.affiliation: 1] Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA. [2] Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Roxane
authors.initials: R
authors.lastname: Tussiwand
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Wumesh
authors.initials: W
authors.lastname: Kc
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Kretzer
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Carlos G
authors.initials: CG
authors.lastname: Briseño
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Vivek
authors.initials: V
authors.lastname: Durai
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Prachi
authors.initials: P
authors.lastname: Bagadia
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Malay
authors.initials: M
authors.lastname: Haldar
authors.affiliation: Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Schönheit
authors.affiliation: Institute of Molecular Tumor Biology, University of Münster, Münster, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Rosenbauer
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Murphy
authors.affiliation: 1] Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA. [2] Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Murphy
mesh_terms: D000818:Animals; D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D051927:CD24 Antigen / Q000276:immunology / Q000378:metabolism; D016827:CD8 Antigens / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D002999:Clone Cells / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D011485:Protein Binding; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D013234:Stem Cells / Q000276:immunology* / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics / Q000276:immunology; D000099185:Interferon Regulatory Factor-8
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D051927:CD24 Antigen; D016827:CD8 Antigens; D050835:Interferon Regulatory Factors; D011971:Receptors, Immunologic; D012097:Repressor Proteins; D000099185:Interferon Regulatory Factor-8; C431698:CD8alpha antigen; C501922:Sirpa protein, mouse; C533289:SNFT protein, mouse