The transcription factor Spi-B regulates human plasmacytoid dendritic cell survival through direct induction of the antiapoptotic gene BCL2-A1

Blood. 2012 May 31;119(22):5191-200. doi: 10.1182/blood-2011-07-370239. Epub 2012 Apr 17.

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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / physiology*
  • Cell Survival / physiology
  • Cells, Cultured
  • Child, Preschool
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Dendritic Cells / cytology
  • Dendritic Cells / metabolism*
  • Female
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism*
  • Humans
  • Infant
  • Male
  • Minor Histocompatibility Antigens
  • Plasma Cells / cytology
  • Plasma Cells / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • BCL2-related protein A1
  • DNA-Binding Proteins
  • Minor Histocompatibility Antigens
  • Proto-Oncogene Proteins c-bcl-2
  • Transcription Factors
  • SPIB protein, human