Function of mouse lectin receptors

在本研究中，我们旨在阐明小鼠C型凝集素SIGNR3和DCIR1的作用。SIGNR3是小鼠DC-SIGN的同源物，识别酵母菌和白色念珠菌。我们建立了新的抗SGINR3的单抗，并原位检测了SIGNR3^+细胞的分布。结果显示，它们定位于真皮、皮下淋巴结和循环血液中。真皮和结节中有两种类型的SIGNR3^+细胞，一种是CD11c^+树突状细胞，另一种是巨噬细胞。在淋巴结中，它们分布在滤泡间区、皮质旁和髓质中的HEV附近。SIGNR3仅在血液中CD115^+Ly6C^；int-low&gt；单核细胞中表达。在炎症反应过程中，在引流结节观察到SIGNR3^+细胞大量增加，尤其是HEV周围。这些结果暗示SIGNR3^+单核细胞可能被募集到炎症组织中。另一方面，免疫印迹和流式细胞术检测到DCIR1不仅表达树突状细胞，还检测到B细胞、中性粒细胞、单核细胞和巨噬细胞的表达。有趣的是，DCIR1分子在稳态时主要存在于细胞质中，在炎性细胞因子和TLR配体的刺激下，表面表达上调，而不进行从头合成。此外，聚集到炎症部位的粒细胞在细胞表面表达丰富的DCIR1。在DMSO刺激HL60细胞后，也观察到类似的现象，诱导其分化为中性粒细胞。DCIR1与SIGNR3具有相同的EPN基序，并被发现与酵母多糖、热灭活的白色念珠菌结合。DCIR1与特异性抗体交联后，与SHP-1和SHP-2发生磷酸化结合。因此，DCIR1介导的信号可能参与了炎症反应的调节。

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.