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

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.

Key words： dendritic cells; CD56⁺ DC; pDC; mDC; BPDCN

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