Critical role of transcription factor PU.1 in the expression of CD80 and CD86 on dendritic cells

Blood. 2011 Feb 17;117(7):2211-22. doi: 10.1182/blood-2010-06-291898. Epub 2010 Nov 30.


In this study, we investigated the role of a transcription factor, PU.1, in the regulation of CD80 and CD86 expression in dendritic cells (DCs). A chromatin immunoprecipitation assay revealed that PU.1 is constitutively bound to the CD80 and CD86 promoters in bone marrow-derived DCs. In addition, co-expression of PU.1 resulted in the transactivation of the CD80 and CD86 promoters in a reporter assay. The binding of PU.1 to cis-enhancing regions was confirmed by electromobility gel-shift assay. As expected, inhibition of PU.1 expression by short interfering RNA (siRNA) in bone marrow-derived DCs resulted in marked down-regulation of CD80 and CD86 expression. Moreover, overexpression of PU.1 in murine bone marrow-derived lineage-negative cells induced the expression of CD80 and CD86 in the absence of monocyte/DC-related growth factors and/or cytokines. Based on these results, we conclude that PU.1 is a critical factor for the expression of CD80 and CD86. We also found that subcutaneous injection of PU.1 siRNA or topical application of a cream-emulsified PU.1 siRNA efficiently inhibited murine contact hypersensitivity. Our results suggest that PU.1 is a potential target for the treatment of immune-related diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Animals
  • B7-1 Antigen / genetics
  • B7-1 Antigen / metabolism*
  • B7-2 Antigen / genetics
  • B7-2 Antigen / metabolism*
  • Base Sequence
  • Binding Sites / genetics
  • DNA, Complementary / genetics
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism*
  • Dermatitis, Contact / genetics
  • Dermatitis, Contact / immunology
  • Dermatitis, Contact / prevention & control
  • Down-Regulation
  • Female
  • In Vitro Techniques
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins / antagonists & inhibitors
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / genetics
  • Trans-Activators / antagonists & inhibitors
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Initiation Site
  • Transcriptional Activation


  • B7-1 Antigen
  • B7-2 Antigen
  • Cd86 protein, mouse
  • DNA, Complementary
  • Proto-Oncogene Proteins
  • RNA, Small Interfering
  • Trans-Activators
  • proto-oncogene protein Spi-1