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

被引:382
作者
Bouchon, A [1 ]
Hernández-Munain, C [1 ]
Cella, M [1 ]
Colonna, M [1 ]
机构
[1] Basel Inst Immunol, CH-4005 Basel, Switzerland
关键词
TREM; activation; human; survival; migration;
D O I
10.1084/jem.194.8.1111
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:1111 / 1122
页数:12
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