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      A Dap12-Mediated Pathway Regulates Expression of Cc Chemokine Receptor 7 and Maturation of Human Dendritic Cells

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          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.

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          Most cited references 71

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          Chemokines: a new classification system and their role in immunity.

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            Rapid detection of octamer binding proteins with 'mini-extracts', prepared from a small number of cells.

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                Author and article information

                Contributors
                Journal
                J Exp Med
                The Journal of Experimental Medicine
                The Rockefeller University Press
                0022-1007
                1540-9538
                15 October 2001
                : 194
                : 8
                : 1111-1122
                Affiliations
                [a ]Basel Institute for Immunology, CH-4005 Basel, Switzerland
                Article
                011154
                2193511
                11602640
                © 2001 The Rockefeller University Press
                Categories
                Original Article

                Medicine

                activation, survival, human, trem, migration

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