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

A. Bouchon, C. Hernández-Munain, M. Cella, M. Colonna

Research output: Contribution to journalArticlepeer-review

340 Scopus citations

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-κB 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.

Original languageEnglish
Pages (from-to)1111-1122
Number of pages12
JournalJournal of Experimental Medicine
Volume194
Issue number8
DOIs
StatePublished - Oct 15 2001

Keywords

  • Activation
  • Human
  • Migration
  • Survival
  • TREM

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