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Original Article |
mcolonna{at}pathology.wustl.edu
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-
B 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.
Key Words: TREM • activation • human • survival • migration
Abbreviations used in this paper: CCR7, CC chemokine receptor 7; DC, dendritic cell; EMSA, electrophoretic mobility assay; ERK, extracellular signal–regulated kinase; HRP, horseradish peroxidase; ITAM, immunoreceptor tyrosine-based activation motif; MAPK, mitogen-activated protein kinase; MDL-1, myeloid DAP12-associating lectin-1; NF, nuclear factor; PTK, protein tyrosine kinase; SAPK, stress-activated protein kinase; SIRP-β, signal-regulatory protein β; TLR, Toll-like receptor; TREM, triggering receptor expressed on myeloid cells.
© 2001 The Rockefeller University Press
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