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
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Research Support, Non-U.S. Gov't
MeSH terms
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Biomarkers / metabolism
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CD56 Antigen / genetics*
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CD56 Antigen / immunology
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Cell Lineage / genetics
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Cell Lineage / immunology
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Dendritic Cells / immunology
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Dendritic Cells / metabolism
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Dendritic Cells / pathology*
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Gene Expression
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Hematologic Neoplasms / genetics
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Hematologic Neoplasms / immunology
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Hematologic Neoplasms / pathology*
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Humans
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Immunophenotyping
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Interferon Type I / biosynthesis
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Interferon Type I / metabolism
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Interleukin-12 / biosynthesis
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Interleukin-12 / metabolism
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Interleukin-3 Receptor alpha Subunit / genetics*
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Interleukin-3 Receptor alpha Subunit / immunology
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Lectins, C-Type / genetics*
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Lectins, C-Type / immunology
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Membrane Glycoproteins / genetics*
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Membrane Glycoproteins / immunology
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Myeloid Cells / immunology
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Myeloid Cells / metabolism
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Myeloid Cells / pathology*
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Receptors, Immunologic / genetics*
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Receptors, Immunologic / immunology
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Terminology as Topic
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Toll-Like Receptor 4 / genetics
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Toll-Like Receptor 4 / immunology
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Toll-Like Receptor 7 / genetics
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Toll-Like Receptor 7 / immunology
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Toll-Like Receptor 9 / genetics
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Toll-Like Receptor 9 / immunology
Substances
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Biomarkers
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CD56 Antigen
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CLEC4C protein, human
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IL3RA protein, human
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Interferon Type I
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Interleukin-3 Receptor alpha Subunit
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Lectins, C-Type
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Membrane Glycoproteins
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NCAM1 protein, human
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Receptors, Immunologic
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TLR4 protein, human
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TLR7 protein, human
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TLR9 protein, human
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Toll-Like Receptor 4
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Toll-Like Receptor 7
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Toll-Like Receptor 9
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Interleukin-12