TY - JOUR
T1 - DCIR is endocytosed into human dendritic cells and inhibits TLR8-mediated cytokine production
AU - Meyer-Wentrup, Friederike
AU - Cambi, Alessandra
AU - Joosten, Ben J.
AU - Looman, Maaike W.
AU - De Jolanda M Vries, I.
AU - Figdor, Carl G.
AU - Adema, Gosse J.
PY - 2009/3/1
Y1 - 2009/3/1
N2 - 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-l and dendritic cell immunoreceptor (DCIR), contain in-tracellular ITIMs or ITAMs. In this study, we explored expression and function of the ITIM-con-taining CLR DCIR on professional APCs. DCIR is expressed on immature and mature monocyte-de-rived DCs (moDC) but also on monocytes, macro-phages, 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 in-ternalization is clathrin-dependent and leads to its localization in the endo-/lysosomal compartment, including lysosome-associated membrane pro- tein-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 cy- tokine 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. copy; Society for Leukocyte Biology.
AB - 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-l and dendritic cell immunoreceptor (DCIR), contain in-tracellular ITIMs or ITAMs. In this study, we explored expression and function of the ITIM-con-taining CLR DCIR on professional APCs. DCIR is expressed on immature and mature monocyte-de-rived DCs (moDC) but also on monocytes, macro-phages, 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 in-ternalization is clathrin-dependent and leads to its localization in the endo-/lysosomal compartment, including lysosome-associated membrane pro- tein-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 cy- tokine 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. copy; Society for Leukocyte Biology.
KW - C-type lectin
KW - Cell surface molecule
KW - Pattern recognition receptor
KW - Receptor cross-talk
UR - http://www.scopus.com/inward/record.url?scp=61449231643&partnerID=8YFLogxK
U2 - 10.1189/jlb.0608352
DO - 10.1189/jlb.0608352
M3 - Article
C2 - 19028959
AN - SCOPUS:61449231643
SN - 0741-5400
VL - 85
SP - 518
EP - 525
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 3
ER -