A DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of human dendritic cells

J Exp Med. 2001 Oct 15;194(8):1111-22. doi: 10.1084/jem.194.8.1111.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Antigens, CD / biosynthesis
  • B7-2 Antigen
  • CD40 Antigens / biosynthesis
  • Cell Differentiation
  • Cell Line
  • Cell Survival
  • DNA-Binding Proteins / metabolism
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects
  • Dendritic Cells / metabolism*
  • Enzyme Activation
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism
  • Histocompatibility Antigens Class II / biosynthesis
  • Humans
  • I-kappa B Proteins*
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Membrane Proteins
  • Mice
  • Mice, Inbred BALB C
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism
  • Monocytes / cytology
  • Monocytes / metabolism
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Receptors, CCR7
  • Receptors, Chemokine / biosynthesis*
  • Receptors, Chemokine / genetics
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • Signal Transduction / physiology*
  • Triggering Receptor Expressed on Myeloid Cells-1
  • Up-Regulation*
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens, CD
  • B7-2 Antigen
  • CCR7 protein, human
  • CD40 Antigens
  • CD86 protein, human
  • Ccr7 protein, mouse
  • Cd86 protein, mouse
  • DNA-Binding Proteins
  • Histocompatibility Antigens Class II
  • I-kappa B Proteins
  • Membrane Glycoproteins
  • Membrane Proteins
  • NF-kappa B
  • NFKBIA protein, human
  • Nfkbia protein, mouse
  • Receptors, CCR7
  • Receptors, Chemokine
  • Receptors, Immunologic
  • TREM1 protein, human
  • TREM2 protein, human
  • TYROBP protein, human
  • Trem2 protein, mouse
  • Triggering Receptor Expressed on Myeloid Cells-1
  • NF-KappaB Inhibitor alpha
  • Protein-Tyrosine Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases