Abstract
Dendritic cells are equipped with lectin receptors to sense the extracellular environment and modulate cellular responses. Human plasmacytoid dendritic cells (pDCs) uniquely express blood dendritic cell antigen 2 (BDCA2) protein, a C-type lectin lacking an identifiable signaling motif. We demonstrate here that BDCA2 forms a complex with the transmembrane adapter Fc epsilon RI gamma. Through pathway analysis, we identified a comprehensive signaling machinery in human pDCs, similar to that which operates downstream of the B cell receptor (BCR), which is distinct from the system involved in T cell receptor (TCR) signaling. BDCA2 crosslinking resulted in the activation of the BCR-like cascade, which potently suppressed the ability of pDCs to produce type I interferon and other cytokines in response to Toll-like receptor ligands. Therefore, by associating with Fc epsilon RI gamma, BDCA2 activates a novel BCR-like signaling pathway to regulate the immune functions of pDCs.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / immunology
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Animals
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B-Lymphocytes / immunology
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Dendritic Cells / immunology*
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Humans
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Interferon Type I / immunology
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Jurkat Cells
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Lectins, C-Type / genetics
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Lectins, C-Type / immunology*
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / immunology*
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Mice
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Multiprotein Complexes / immunology
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NF-kappa B / immunology
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Oligonucleotide Array Sequence Analysis
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Receptors, Antigen, B-Cell / genetics
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Receptors, Antigen, B-Cell / immunology*
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Receptors, IgE / genetics
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Receptors, IgE / immunology*
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Receptors, Immunologic / genetics
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Receptors, Immunologic / immunology*
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Signal Transduction / physiology*
Substances
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Adaptor Proteins, Signal Transducing
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B cell linker protein
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CLEC4C protein, human
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Interferon Type I
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Lectins, C-Type
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Membrane Glycoproteins
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Multiprotein Complexes
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NF-kappa B
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Receptors, Antigen, B-Cell
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Receptors, IgE
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Receptors, Immunologic