A. Bouchon et al., A DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of human dendritic cells, J EXP MED, 194(8), 2001, pp. 1111-1122
Gene targeting of the adaptor molecule DAP12 in mice caused abnormal distri
bution and impaired antigen presentation capacity of dendritic cells (DCs).
However, the DAP12-associated receptors expressed on DCs and their functio
ns 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 m
onocyte-derived DCs, which is associated with DAP12. TREM-2/DAP12 promotes
upregulation of CC chemokine receptor 7, partial DC maturation, and DC surv
ival through activation of protein tyrosine kinases and extracellular signa
l-regulated kinase. In contrast to Toll-like receptor-mediated signaling, T
REM2/DAP12 stimulation is independent of nuclear factor-kappaB and p38 stre
ss-activated protein kinase. This novel DC activation pathway may regulate
DC homeostasis. and amplify DC responses to pathogens, explaining the pheno
type observed in DAP12-deficient mice.