Human BDCA2+CD123+CD56+ dendritic cells (DCs) related to blastic plasmacytoid dendritic cell neoplasm represent a unique myeloid DC subset

Protein Cell. 2015 Apr;6(4):297-306. doi: 10.1007/s13238-015-0140-x. Epub 2015 Mar 18.

Abstract

Dendritic cells (DCs) comprise two functionally distinct subsets: plasmacytoid DCs (pDCs) and myeloid DCs (mDCs). pDCs are specialized in rapid and massive secretion of type I interferon (IFN-I) in response to nucleic acids through Toll like receptor (TLR)-7 or TLR-9. In this report, we characterized a CD56(+) DC population that express typical pDC markers including CD123 and BDCA2 but produce much less IFN-I comparing with pDCs. In addition, CD56(+) DCs cluster together with mDCs but not pDCs by genome-wide transcriptional profiling. Accordingly, CD56(+) DCs functionally resemble mDCs by producing IL-12 upon TLR4 stimulation and priming naïve T cells without prior activation. These data suggest that the CD56(+) DCs represent a novel mDC subset mixed with some pDC features. A CD4(+)CD56(+) hematological malignancy was classified as blastic plasmacytoid dendritic cell neoplasm (BPDCN) due to its expression of characteristic molecules of pDCs. However, we demonstrated that BPDCN is closer to CD56(+) DCs than pDCs by global gene-expression profiling. Thus, we propose that the CD4(+)CD56(+) neoplasm may be a tumor counterpart of CD56(+) mDCs but not pDCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / metabolism
  • CD56 Antigen / genetics*
  • CD56 Antigen / immunology
  • Cell Lineage / genetics
  • Cell Lineage / immunology
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Dendritic Cells / pathology*
  • Gene Expression
  • Hematologic Neoplasms / genetics
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / pathology*
  • Humans
  • Immunophenotyping
  • Interferon Type I / biosynthesis
  • Interferon Type I / metabolism
  • Interleukin-12 / biosynthesis
  • Interleukin-12 / metabolism
  • Interleukin-3 Receptor alpha Subunit / genetics*
  • Interleukin-3 Receptor alpha Subunit / immunology
  • Lectins, C-Type / genetics*
  • Lectins, C-Type / immunology
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / immunology
  • Myeloid Cells / immunology
  • Myeloid Cells / metabolism
  • Myeloid Cells / pathology*
  • Receptors, Immunologic / genetics*
  • Receptors, Immunologic / immunology
  • Terminology as Topic
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / immunology
  • Toll-Like Receptor 7 / genetics
  • Toll-Like Receptor 7 / immunology
  • Toll-Like Receptor 9 / genetics
  • Toll-Like Receptor 9 / immunology

Substances

  • Biomarkers
  • CD56 Antigen
  • CLEC4C protein, human
  • IL3RA protein, human
  • Interferon Type I
  • Interleukin-3 Receptor alpha Subunit
  • Lectins, C-Type
  • Membrane Glycoproteins
  • NCAM1 protein, human
  • Receptors, Immunologic
  • TLR4 protein, human
  • TLR7 protein, human
  • TLR9 protein, human
  • Toll-Like Receptor 4
  • Toll-Like Receptor 7
  • Toll-Like Receptor 9
  • Interleukin-12