Spi-B is critical for plasmacytoid dendritic cell function and development

Blood. 2012 Dec 6;120(24):4733-43. doi: 10.1182/blood-2012-06-436527. Epub 2012 Oct 11.


Plasmacytoid dendritic cells (pDCs), originating from hematopoietic progenitor cells in the BM, are a unique dendritic cell subset that can produce large amounts of type I IFNs by signaling through the nucleic acid-sensing TLR7 and TLR9 (TLR7/9). The molecular mechanisms for pDC function and development remain largely unknown. In the present study, we focused on an Ets family transcription factor, Spi-B, that is highly expressed in pDCs. Spi-B could transactivate the type I IFN promoters in synergy with IFN regulatory factor 7 (IRF-7), which is an essential transcription factor for TLR7/9-induced type I IFN production in pDCs. Spi-B-deficient pDCs and mice showed defects in TLR7/9-induced type I IFN production. Furthermore, in Spi-B-deficient mice, BM pDCs were decreased and showed attenuated expression of a set of pDC-specific genes whereas peripheral pDCs were increased; this uneven distribution was likely because of defective retainment of mature nondividing pDCs in the BM. The expression pattern of cell-surface molecules in Spi-B-deficient mice indicated the involvement of Spi-B in pDC development. The developmental defects of pDCs in Spi-B-deficient mice were more prominent in the BM than in the peripheral lymphoid organs and were intrinsic to pDCs. We conclude that Spi-B plays critical roles in pDC function and development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Bone Marrow Cells / metabolism*
  • Bone Marrow Cells / physiology
  • Dendritic Cells / metabolism*
  • Dendritic Cells / physiology
  • Flow Cytometry
  • Gene Expression Profiling*
  • HEK293 Cells
  • Humans
  • Interferon Type I / genetics
  • Interferon Type I / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Molecular Sequence Data
  • Mutation
  • Oligonucleotide Array Sequence Analysis
  • Promoter Regions, Genetic / genetics
  • Proto-Oncogene Proteins c-ets / genetics*
  • Proto-Oncogene Proteins c-ets / metabolism
  • Proto-Oncogene Proteins c-ets / physiology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Toll-Like Receptor 7 / genetics
  • Toll-Like Receptor 7 / physiology
  • Toll-Like Receptor 9 / genetics
  • Toll-Like Receptor 9 / physiology
  • Transcriptional Activation


  • Interferon Type I
  • Proto-Oncogene Proteins c-ets
  • Spi-B protein, mouse
  • Toll-Like Receptor 7
  • Toll-Like Receptor 9