期刊
JOURNAL OF LEUKOCYTE BIOLOGY
卷 85, 期 3, 页码 518-525出版社
WILEY
DOI: 10.1189/jlb.0608352
关键词
cell surface molecule; pattern recognition receptor; C-type lectin; receptor cross-talk
资金
- Deutsche Forschungsgemeinschaft [ME 2051/2-1]
- Netherlands Organization for Scientific Research [ZonMw 912.02.034, 912.06.030, 916.66.028]
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-alpha 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. J. Leukoc. Biol. 85: 518-525; 2009.
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