title: The transcription factor Spi-B regulates human plasmacytoid dendritic cell survival through direct induction of the antiapoptotic gene BCL2-A1.
abstract: Plasmacytoid dendritic cells (pDCs) selectively express Toll-like receptor (TLR)-7 and TLR-9, which allow them to rapidly secrete massive amounts of type I interferons after sensing nucleic acids derived from viruses or bacteria. It is not completely understood how development and function of pDCs are controlled at the transcriptional level. One of the main factors driving pDC development is the ETS factor Spi-B, but little is known about its target genes. Here we demonstrate that Spi-B is crucial for the differentiation of hematopoietic progenitor cells into pDCs by controlling survival of pDCs and its progenitors. In search for Spi-B target genes, we identified the antiapoptotic gene Bcl2-A1 as a specific and direct target gene, thereby consolidating the critical role of Spi-B in cell survival.
authors.affiliation: Department of Cell Biology and Histology, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Julien J
authors.initials: JJ
authors.lastname: Karrich
authors.forename: Melania
authors.initials: M
authors.lastname: Balzarolo
authors.forename: Heike
authors.initials: H
authors.lastname: Schmidlin
authors.forename: Marion
authors.initials: M
authors.lastname: Libouban
authors.forename: Maho
authors.initials: M
authors.lastname: Nagasawa
authors.forename: Rebecca
authors.initials: R
authors.lastname: Gentek
authors.forename: Shimeru
authors.initials: S
authors.lastname: Kamihira
authors.forename: Takahiro
authors.initials: T
authors.lastname: Maeda
authors.forename: Derk
authors.initials: D
authors.lastname: Amsen
authors.forename: Monika C
authors.initials: MC
authors.lastname: Wolkers
authors.forename: Bianca
authors.initials: B
authors.lastname: Blom
mesh_terms: D002454:Cell Differentiation / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007223:Infant; D008297:Male; D015778:Minor Histocompatibility Antigens; D010950:Plasma Cells / Q000166:cytology / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C096816:BCL2-related protein A1; D004268:DNA-Binding Proteins; D015778:Minor Histocompatibility Antigens; D019253:Proto-Oncogene Proteins c-bcl-2; D014157:Transcription Factors; C076877:SPIB protein, human