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Blood, 15 June 2007, Vol. 109, No. 12, pp. 5371-5379.
Prepublished online as a Blood First Edition Paper on March 1, 2007; DOI 10.1182/blood-2006-08-038422.
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IMMUNOBIOLOGY
Functional specialization of human circulating CD16 and CD1c myeloid dendritic-cell subsets
Diego Piccioli1,
Simona Tavarini1,
Erica Borgogni1,
Veronica Steri1,
Sandra Nuti1,
Chiara Sammicheli1,
Monia Bardelli2,
Daniela Montagna3,
Franco Locatelli3, and
Andreas Wack1
1 Molecular Immunology Department, Research Center, Novartis Vaccines, Siena, Italy;
2 Molecular Biology Department, Università degli Studi, Siena, Italy;
3 Department of Pediatrics, University of Pavia, Pediatric Hematology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy
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- (TNF-)/IL-6/CCL3 (MIP-1)/CCL4 (MIP-1ß)/IL-1ß. CXCL8 (IL-8) is the predominant cytokine produced by CD1c-mDCs on TLR engagement, whereas all other cytokines, particularly TNF-, 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- 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.
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