Abstract
Death receptor 6 is a novel plasmacytoid dendritic cell-specific receptor and modulates type I interferon production.
Highlights
Mono DCDependent manner, whereas there was little induction of IFN-α4 promoters activity when Death receptor 6 (DR6)-EX was overexpressed (Fig. 2F)
Plasmacytoid dendritic cells are the professional type I interferon-producing cells of the immune system, which rapidly produce massive amounts of type I interferons (IFN-I) in response to viruses or other nucleic acids ligands through selectively expressed toll-like receptor (TLR)-7 and TLR9 (Siegal et al, 1999)
We found that Death receptor 6 (DR6) was highly expressed in human Plasmacytoid dendritic cells (pDCs) comparing with other blood cells by microarray analysis (Fig. 1A)
Summary
Dependent manner, whereas there was little induction of IFN-α4 promoters activity when DR6-EX was overexpressed (Fig. 2F). It is well established that IRF7 nuclear translocation is the key event upon stimulation pDCs with CpG-ODN, which eventually leads to the production of IFN-I (Honda et al, 2005a; Honda et al, 2005b). After CpG-ODN stimulation, IRF7 displayed increased distribution in the nucleus, while knockdown of DR6 in GEN2.2 cells significantly diminished the nuclear localization of IRF7 (Fig. 2G). This result suggests that DR6 is necessary for CpG-ODN induced IRF7 nuclear translocation. We demonstrated that knockdown DR6 by shRNA in human pDCs cell line GEN2.2 significantly diminished the CpGODN induced IRF7 nuclear localization and IFN-I production. N-terminal of amyloid precursor protein (N-APP) was identified as a DR6 ligand, leading to caspase-3 activation in DR6 expression and functions in pDCs
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