Signaling and immune regulatory role of the dendritic cell immunoreceptor (DCIR) family lectins: DCIR, DCAR, dectin-2 and BDCA-2

This review focuses on a distinct family of dendritic cells (DC) expressing C-type lectins that include DC immunoreceptor (DCIR), DC immunoactivating receptor (DCAR), DC-associated C-type lectin (dectin)-2 and blood DC antigen (BDCA)-2. DCIR is a type II C-type lectin expressed on antigen presenting cells and granulocytes and acts as an inhibitory receptor via an intracellular immunoreceptor tyrosine-based inhibitory motif (ITIM). In contrast, DCAR has been identified as a molecule that forms a putative pair with DCIR. While both molecules share the highly homologous extracellular lectin domain, DCAR lacks the ITIM in its short cytoplasmic tail and acts as an activating receptor through association with the Fc receptor γ chain. Two other lectins, dectin-2 and BDCA-2, are highly related to DCAR by similarities of their amino acid sequence, molecular structure and chromosomal localization. Although they also lack the ITIM, they are capable of transducing signal to regulate cellular functions positively or negatively. Here we propose to designate these four highly related molecules as the “DCIR family lectins” and discuss their signaling mechanisms, carbohydrate recognition, and other features that contribute to the function of DC to control immunity.