Abstract
Gene targeting of the adaptor molecule DAP12 in mice caused abnormal distribution and impaired antigen presentation capacity of dendritic cells (DCs). However, the DAP12-associated receptors expressed on DCs and their functions have not been identified yet. Here we show that the triggering receptor expressed on myeloid cells-2 (TREM-2) is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12. TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC maturation, and DC survival through activation of protein tyrosine kinases and extracellular signal-regulated kinase. In contrast to Toll-like receptor-mediated signaling, TREM2/DAP12 stimulation is independent of nuclear factor-kappaB and p38 stress-activated protein kinase. This novel DC activation pathway may regulate DC homeostasis and amplify DC responses to pathogens, explaining the phenotype observed in DAP12-deficient mice.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Animals
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Antigens, CD / biosynthesis
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B7-2 Antigen
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CD40 Antigens / biosynthesis
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Cell Differentiation
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Cell Line
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Cell Survival
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DNA-Binding Proteins / metabolism
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Dendritic Cells / cytology
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Dendritic Cells / drug effects
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Dendritic Cells / metabolism*
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Enzyme Activation
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Hematopoietic Stem Cells / cytology
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Hematopoietic Stem Cells / metabolism
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Histocompatibility Antigens Class II / biosynthesis
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Humans
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I-kappa B Proteins*
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Membrane Glycoproteins / biosynthesis
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism*
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Membrane Proteins
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Mice
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Mice, Inbred BALB C
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases / antagonists & inhibitors
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Mitogen-Activated Protein Kinases / metabolism
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Monocytes / cytology
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Monocytes / metabolism
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NF-KappaB Inhibitor alpha
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NF-kappa B / antagonists & inhibitors
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NF-kappa B / metabolism
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Protein-Tyrosine Kinases / antagonists & inhibitors
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Receptors, CCR7
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Receptors, Chemokine / biosynthesis*
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Receptors, Chemokine / genetics
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Receptors, Immunologic / genetics
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Receptors, Immunologic / metabolism*
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Signal Transduction / physiology*
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Triggering Receptor Expressed on Myeloid Cells-1
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Up-Regulation*
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p38 Mitogen-Activated Protein Kinases
Substances
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Adaptor Proteins, Signal Transducing
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Antigens, CD
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B7-2 Antigen
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CCR7 protein, human
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CD40 Antigens
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CD86 protein, human
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Ccr7 protein, mouse
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Cd86 protein, mouse
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DNA-Binding Proteins
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Histocompatibility Antigens Class II
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I-kappa B Proteins
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Membrane Glycoproteins
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Membrane Proteins
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NF-kappa B
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NFKBIA protein, human
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Nfkbia protein, mouse
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Receptors, CCR7
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Receptors, Chemokine
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Receptors, Immunologic
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TREM1 protein, human
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TREM2 protein, human
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TYROBP protein, human
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Trem2 protein, mouse
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Triggering Receptor Expressed on Myeloid Cells-1
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NF-KappaB Inhibitor alpha
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Protein-Tyrosine Kinases
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases