Functional specialization of human circulating CD16 and CD1c myeloid dendritic-cell subsets

Diego Piccioli, Simona Tavarini, Erica Borgogni, Veronica Steri, Sandra Nuti, Chiara Sammicheli, Monia Bardelli, Daniela Montagna, Franco Locatelli, Andreas Wack

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Abstract

Human blood contains 2 populations of dendritic cells (DCs): plasmacytoid and myeloid (mDC). mDCs are subdivided into 3 subsets using the surface markers CD16, CD1c, and BDCA-3. Their role as pathogen sentinels and adjuvant targets was tested by phenotypic and functional analysis. We show that mDC subsets are immature and express mRNA for most toll-like receptors (TLRs), except for TLR3 in CD16-mDCs. The most represented subsets, CD16- and CD1c-mDCs, are similarly responsive to all TLR agonists. Among 31 cytokines tested, both subsets produce CXCL8 (IL-8)/tumor necrosis factor-α (TNF-α)/IL-6/CCL3 (MIP-1α)/CCL4 (MIP-1β)/IL-1β. CXCL8 (IL-8) is the predominant cytokine produced by CD1c-mDCs on TLR engagement, whereas all other cytokines, particularly TNF-α, are secreted in 10-fold to 100-fold higher amounts by CD16-mDCs. CD16-mDCs cocultured with human umbilical vein endothelial cells induce a significantly higher production of CXCL10 (IP-10), granulocyte- macrophage colony-stimulating factor, and granulocyte colony-stimulating factor than CD1c-mDCs. In addition, interleukin-3 and type I interferons are stimuli specifically for DC maturation rather than cytokine secretion, whereas TNF-α is almost ineffective in inducing either function, suggesting a mechanism of T-cell-DC crosstalk and of rapid induction of antigen-presenting cell function during viral infection rather than inflammation. In conclusion, CD16-mDCs show strong proinflammatory activity, whereas CD1c-mDCs appear to be mainly inducers of chemotaxis.

Original languageEnglish
Pages (from-to)5371-5379
Number of pages9
JournalBlood
Volume109
Issue number12
DOIs
Publication statusPublished - Jun 15 2007

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ASJC Scopus subject areas

  • Hematology

Cite this

Piccioli, D., Tavarini, S., Borgogni, E., Steri, V., Nuti, S., Sammicheli, C., Bardelli, M., Montagna, D., Locatelli, F., & Wack, A. (2007). Functional specialization of human circulating CD16 and CD1c myeloid dendritic-cell subsets. Blood, 109(12), 5371-5379. https://doi.org/10.1182/blood-2006-08-038422