Functional specialization of human circulating CD16 and CD1c myeloid dendritic-cell subsets.
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-alpha (TNF-alpha)/IL-6/CCL3 (MIP-1 alpha)/CCL4 (MIP-1beta)/IL-1 beta. CXCL8 (IL-8) is the predominant cytokine produced by CD1c-mDCs on TLR engagement, whereas all other cytokines, particularly TNF-alpha, 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-alpha 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.
Piccioli
Diego
D
Molecular Immunology Department, Research Center, Novartis Vaccines, Siena, Italy.
Tavarini
Simona
S
Borgogni
Erica
E
Steri
Veronica
V
Nuti
Sandra
S
Sammicheli
Chiara
C
Bardelli
Monia
M
Montagna
Daniela
D
Locatelli
Franco
F
Wack
Andreas
A
D018949:Antigens, CD1; D002450:Cell Communication / Q000276:immunology; D002633:Chemotaxis; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology / Q000502:physiology*; D042783:Endothelial Cells / Q000166:cytology; D004730:Endothelium, Vascular; D006801:Humans; D007249:Inflammation; D022423:Myeloid Cells; D017452:Receptors, IgG
D018949:Antigens, CD1; D016207:Cytokines; D017452:Receptors, IgG