DCIR Acts as an Inhibitory Receptor Depending on its Immunoreceptor Tyrosine-Based Inhibitory Motif

Major histocompatibility complex class II positive cells, namely dendritic cells, monocytes/macrophages, and B cells, are categorized as antigen-presenting cells. Dendritic cells, so-called professional antigen-presenting cells, use distinct sets of surface receptors before and after maturation: those to capture antigens and those to interact with T cells, respectively. But there remain many surface molecules whose functions are still unknown. In this study, we isolated dendritic cell immunoreceptor from mouse bone-marrow-derived mature dendritic cells. Dendritic cell immunoreceptor is a recently reported C-type lectin receptor characteristic with cytoplasmic immunoreceptor tyrosine-based inhibitory motif. Expression of mouse dendritic cell immunoreceptor mRNA was observed specifically in spleen and lymph node, slightly increased with dendritic cell maturation during in vitro culture of bone marrow cells, and was not detected in cultured natural killer cells. Surface expression of mouse dendritic cell immunoreceptor protein was observed in splenic antigen-presenting cells including B cells, monocytes/macrophages, and dendritic cells, but not in T cells. To reveal the downregulating capacity of dendritic cell immunoreceptor in antigen-presenting cells, the change of B-cell-receptor-mediated signals after coligation with a chimeric Fcgamma receptor IIB containing the cytoplasmic portion of mouse dendritic cell immunoreceptor was examined. As a result, we detected two distinct inhibitory effects of cytoplasmic dendritic cell immunoreceptor minus sign inhibition of B-cell-receptor-mediated Ca2+ mobilization and protein tyrosine phosphorylation minus sign and both of these effects required the tyrosine residue inside the immunoreceptor tyrosine-based inhibitory motif. This report presents immunoreceptor tyrosine-based inhibitory motif-dependent negative regulatory function of dendritic cell immunoreceptors. In conclusion, mouse dendritic cell immunoreceptor expressed on antigen-presenting cells can exert two distinct inhibitory signals depending on its immunoreceptor tyrosine-based inhibitory motif tyrosine residue.