DCIR is endocytosed into human dendritic cells and inhibits TLR8-mediated cytokine production

C‐type lectin receptors (CLRs) expressed on APCs play a pivotal role in the immune system as pattern‐recognition and antigen‐uptake receptors. In addition, they may signal directly, leading to cytokine production and immune modulation. To this end, some CLRs, like dectin‐1 and dendritic cell immunor...

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Bibliographic Details
Published in:Journal of leukocyte biology 2009-03, Vol.85 (3), p.518-525
Main Authors: Meyer‐Wentrup, Friederike, Cambi, Alessandra, Joosten, Ben, Looman, Maaike W., Vries, I. Jolanda M., Figdor, Carl G., Adema, Gosse J.
Format: Article
Language:English
Subjects:
cell surface molecule
Cells, Cultured
C‐type lectin
Dendritic Cells - immunology
Dendritic Cells - metabolism
Endocytosis - immunology
Endosomes
Humans
Interleukin-12 - antagonists & inhibitors
Lectins, C-Type - metabolism
Lectins, C-Type - physiology
Lysosomes
Membrane Glycoproteins - metabolism
Membrane Glycoproteins - physiology
pattern recognition receptor
Receptor Cross-Talk - immunology
receptor cross‐talk
Receptors, Immunologic - metabolism
Receptors, Immunologic - physiology
Toll-Like Receptor 8 - immunology
Tumor Necrosis Factor-alpha - antagonists & inhibitors
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Summary:C‐type lectin receptors (CLRs) expressed on APCs play a pivotal role in the immune system as pattern‐recognition and antigen‐uptake receptors. In addition, they may signal directly, leading to cytokine production and immune modulation. To this end, some CLRs, like dectin‐1 and dendritic cell immunoreceptor (DCIR), contain intracellular ITIMs or ITAMs. In this study, we explored expression and function of the ITIM‐containing CLR DCIR on professional APCs. DCIR is expressed on immature and mature monocyte‐derived DCs (moDC) but also on monocytes, macrophages, B cells, and freshly isolated myeloid and plasmacytoid DCs. We show that endogenous DCIR is internalized efficiently into human moDC after triggering with DCIR‐specific mAb. DCIR internalization is clathrin‐dependent and leads to its localization in the endo‐/lysosomal compartment, including lysosome‐associated membrane protein‐1+ lysosomes. DCIR triggering affected neither TLR4‐ nor TLR8‐mediated CD80 and CD86 up‐regulation. Interestingly, it did inhibit TLR8‐mediated IL‐12 and TNF‐α production significantly, and TLR2‐, TLR3‐, or TLR4‐induced cytokine production was not affected. Collectively, the data presented characterize DCIR as an APC receptor that is endocytosed efficiently in a clathrin‐dependent manner and negatively affects TLR8‐mediated cytokine production. These data provide further support to the concept of CLR/TLR cross‐talk in modulating immune responses.
ISSN:0741-5400
1938-3673
DOI:10.1189/jlb.0608352