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

Piccioli D, Tavarini S, Borgogni E, Steri V, Nuti S, Sammicheli C, Bardelli M, Montagna D, Locatelli F, Wack A.
Blood. 109:5371-9 (2007)

Human blood contains two populations of dendritic cells (DCs) termed plasmacytoid and myeloid. Myeloid DCs (mDCs) are subdivided into three subsets using the surface markers CD16, CD1c, and BDCA-3. Their differential role as pathogen sentinels and adjuvant targets was tested by extensive phenotypic and functional analysis. We show that mDC subsets are immature and express mRNA for most 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)/TNF-/IL-6/CCL3(MIP-1)/CCL4(MIP-1)/IL-1. CXCL8(IL-8) is the predominant cytokine produced by CD1c-mDCs upon TLR engagement, whereas all other cytokines, particularly TNF-, are secreted in 10-fold to 100-fold higher amounts by CD16-mDCs. In addition, CD16-mDCs co-cultured with HUVECs induce a significantly higher production of CXCL10(IP-10), GM-CSF and G-CSF than CD1c-mDCs. We also show that IL-3 and type-I interferons are stimuli specifically for DC maturation rather than cytokine secretion, while TNF- is almost ineffective in inducing either function, suggesting a possible mechanism of T cell-DC cross-talk and of rapid induction of APC function during viral infection rather than inflammation. In conclusion CD16-mDCs show strong pro-inflammatory activity, while CD1c-mDCs appear to be mainly inducers of chemotaxis.

Pub Med: http://www.ncbi.nlm.nih.gov/pubmed/17332250

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