A member of the calcium-dependent (C-type) lectin receptor (CLR) family, DCIR (for dendritic cell (DC) immunoreceptor), is a type II membrane glycoprotein of 237aa with a single carbohydrate recognition domain (CRD), closest in homology to those of the macrophage lectin and hepatic asialoglycoprotein receptors. The intracellular domain of DCIR contains a consensus immunoreceptor tyrosine-based inhibitory motif (ITIM). A mouse cDNA, encoding a homologous protein has been identified. Northern blot analysis shows that DCIR mRNA is predominantly transcribed in hematopoietic tissues. DCIR displays a typical lectin CRD and is expressed on DCs, monocytes, macrophages, B lymphocytes, and granulocytes, but not detected on NK and T cells. DCIR is strongly expressed by DCs derived from blood monocytes cultured with GM-CSF and IL-4. DCIR is preferentially expressed by monocyte-related rather than Langerhans cell related DCs obtained from CD34+ progenitor cells. Finally, DCIR expression is down-regulated by signals inducing DC maturation such as CD40 ligand, LPS, or TNF-alpha. Thus, DCIR is differentially expressed on DCs depending on their origin and stage of maturation:activation. DCIR represents a novel surface molecule expressed by antigen-presenting cells, and of potential importance in regulation of DC function.