| Research Abstract |
In this study, we aimed to elucidate role of mouse C-type lectins, SIGNR3 and DCIR1. SIGNR3 is a homologue of mouse DC-SIGN and recognizes zymosan and C. albicans. We established new monoclonals antibody specific for SGINR3 and examined the distribution of SIGNR3^+ cells in situ. They were shown to localize in dermis, subcutaneous lymph nodes, and circulating blood. There were two types of SIGNR3^+ cells in the dermis and node ; one was CD11c^+ dendritic cells and the other macrophages. In lymph nodes, they were distributed in interfollicular regions, near HEV in paracortex and medulla. SIGNR3 is expressed only in CD115^+ Ly6C^<int-low> monocytes in the blood. During inflammatory response, a large increase in SIGNR3^+ cells is observed in draining nodes, particularly around HEV. These results imply the possibility that SIGNR3^+ monocytes are recruited into inflamed tissue. This study aimed to examine this possibility.
On the other hand, expression of DCIR1, which is characterized by the presence of ITIM in its cytoplasmic portion, was detected not only dendritic cells, but also B cells, neutrophil, monocytes and macrophages by Western blot and flowcytometry. Interestingly, DCIR1 molecules were present mainly in cytoplasm in the steady state and the surface expression was up-regulated by the stimulation with inflammatory cytokines and TLR ligands without de novo synthesis. In addition, granulocytes recruited into inflammatory site expressed abundant DCIR1 on cell surface. Similar phenomenon was also observed in HL60 cells after stimulation with DMSO that induces differentiation to neutrophil. DCIR1 shared EPN motif with SIGNR3 and was found to bind to zymosan, heat-killed and live C. albicans. Upon cross-linking with specific antibody, DCIR1 was phosphorylated and associated with SHP-1 and SHP-2. Therefore, DCIR1-mediated signal may be involved in the regulation of inflammatory response.
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