Dendritic cell immunoreceptors: C-type lectin receptors for pattern-recognition and signaling on antigen-presenting cells

C-type lectin receptors are equipped on phagocytes for antigen capturing. Some of them seem to have a major role in cellular activation, rather than antigen internalization. The dendritic cell (DC) immunoreceptor (DCIR) and DC-associated C-type lectin (dectin)-1 have been identified as prototypic DC-associated C-type lectin receptors, characterized by their signaling mechanisms through distinct intracellular motifs; the former contains the immunoreceptor tyrosine-based inhibitory motif (ITIM), to act as an inhibitory receptor, whereas the latter works as an activating receptor via its immunoreceptor tyrosine-based activation motif (ITAM). Genes of both receptors are localized very close to the natural killer (NK) gene complex (NKC), in which genes of lectin-type activating and inhibitory NK cell receptors are clustered. Recently, the gene of the DC immunoactivating receptor (DCAR) has been identified next to the DCIR gene, and this acts as a putative activating pair of DCIR through association with an ITAM-bearing Fc receptor (FcR) γ chain. On the other hand, the gene of an ITIM-bearing myeloid inhibitory C-type lectin-like receptor (MICL) has been found close to the dectin-1 gene. The genes of other homologous DC-associated C-type lectin receptors, dectin-2 and blood DC antigen (BDCA)-2, form a cluster with those of DCIR and DCAR, while the dectin-1 gene cluster contains lectin-like oxidized low-density lipoprotein receptor (LOX)-1, C-type lectin-like receptor (CLEC)-1 and 2, as well as MICL. Although no ligand of DCIR has yet been identified, dectin-1 recognizes fungal β-glucan and its critical role in the biological effects of β-glucan has been vigorously investigated. In this review, the characteristic features of these DCIR and dectin-1 family lectins, including the signaling mechanisms, ligand recognition and regulation of cellular functions, are summarized and the term “DC immunoreceptors” is applied to a distinct set of signaling pattern-recognition receptors described here. C-type lectin receptors are equipped on phagocytes for antigen capturing. Some of them seem to have a major role in cellular activation, rather than antigen internalization. The dendritic cell (DC) immunoreceptor (DCIR) and DC-associated C-type lectin (dectin)-1 have been identified as prototypic DC-associated C-type lectin receptors, characterized by their signaling mechanisms through distinct intracellular motifs; the former contains the immunoreceptor tyrosine-based inhibitory motif (ITIM), to act as an inhibitory receptor, whereas the latter works as an activating receptor via its immunoreceptor tyrosine-based activation motif (ITAM). Genes of both receptors are localized very close to the natural killer (NK) gene complex (NKC), in which genes of lectin-type activating and inhibitory NK cell receptors are clustered. Recently, the gene of the DC immunoactivating receptor (DCAR) has been identified next to the DCIR gene, and this acts as a putative activating pair of DCIR through association with an ITAM-bearing Fc receptor (FcR) γ chain. On the other hand, the gene of an ITIM-bearing myeloid inhibitory C-type lectin-like receptor (MICL) has been found close to the dectin-1 gene. The genes of other homologous DC-associated C-type lectin receptors, dectin-2 and blood DC antigen (BDCA)-2, form a cluster with those of DCIR and DCAR, while the dectin-1 gene cluster contains lectin-like oxidized low-density lipoprotein receptor (LOX)-1, C-type lectin-like receptor (CLEC)-1 and 2, as well as MICL. Although no ligand of DCIR has yet been identified, dectin-1 recognizes fungal β-glucan and its critical role in the biological effects of β-glucan has been vigorously investigated. In this review, the characteristic features of these DCIR and dectin-1 family lectins, including the signaling mechanisms, ligand recognition and regulation of cellular functions, are summarized and the term “DC immunoreceptors” is applied to a distinct set of signaling pattern-recognition receptors described here. Nobuo Kanazawa graduated and received the MD degree from Kyoto University Faculty of Medicine in 1994 and was trained at the Department of Dermatology. From 1996, he studied molecular biology and immunology at the Department of Molecular Biology of Kyoto University Graduate School of Medicine (Prof. T. Honjo) and obtained the PhD degree in 2000. He was a staff of the Department of Dermatology, Kyoto University Graduate School of Medicine from 2001 to 2005. Since 2003, he spent almost 2 years as a postdoctoral research fellow at the Department of Dermatology, University of Erlangen, Germany (Prof. G. Schuler). In 2006, he moved to Wakayama Medical University, where he is an assistant professor in the Department of Dermatology.