Targeting DCIR on human plasmacytoid dendritic cells results in antigen presentation and inhibits IFN-alpha production.

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Publication year
2008Source
Blood, 111, 8, (2008), pp. 4245-53ISSN
Publication type
Article / Letter to editor

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Organization
Tumorimmunology
Medical Oncology
Journal title
Blood
Volume
vol. 111
Issue
iss. 8
Page start
p. 4245
Page end
p. 53
Subject
N4i 1: Pathogenesis and modulation of inflammation; NCMLS 1: Immunity, infection and tissue repair; NCMLS 2: Immune Regulation; ONCOL 1: Hereditary cancer and cancer-related syndromes; ONCOL 3: Translational research; UMCN 1.4: Immunotherapy, gene therapy and transplantationAbstract
C-type lectin receptors (CLRs) fulfill multiple functions within the immune system by recognition of carbohydrate moieties on foreign or (altered) self-structures. CLRs on myeloid dendritic cells (DCs) have been well characterized as pattern-recognition receptors (PRRs) combining ligand internalization with complex signaling events. Much less is known about CLR expression and function in human plasmacytoid DCs (pDCs), the major type I interferon (IFN) producers. In this study, we demonstrate that, next to the CLR BDCA-2, human pDCs express DC immunoreceptor (DCIR), a CLR with putative immune-inhibitory function, but not dectin-1, mannose receptor, or DC-specific ICAM-3-grabbing nonintegrin. DCIR surface levels are reduced on pDC maturation after TLR9 triggering. Interestingly, DCIR triggering inhibits TLR9-induced IFN-alpha production while leaving up-regulation of costimulatory molecule expression unaffected. Furthermore, DCIR is readily internalized into pDCs after receptor triggering. We show that DCIR internalization is clathrin-dependent because it can be inhibited by hypertonic shock and dominant-negative dynamin. Importantly, antigens targeted to pDCs via DCIR are presented to T cells. These findings indicate that targeting DCIR on pDCs not only results in efficient antigen presentation but also affects TLR9-induced IFN-alpha production. Collectively, the data show that targeting of DCIR can modulate human pDC function and may be applied in disease prevention and treatment.
This item appears in the following Collection(s)
- Academic publications [227437]
- Electronic publications [107154]
- Faculty of Medical Sciences [86157]
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