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

Abstract

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) gamma 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 beta-glucan and its critical role in the biological effects of beta-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.