APCs express DCIR, a novel C-type lectin surface receptor containing an immunoreceptor tyrosine-based inhibitory motif.
We have identified a novel member of the calcium-dependent (C-type) lectin family. This molecule, designated DCIR (for dendritic cell (DC) immunoreceptor), is a type II membrane glycoprotein of 237 aa 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. A mouse cDNA, encoding a homologous protein has been identified. Northern blot analysis showed DCIR mRNA to be predominantly transcribed in hematopoietic tissues. The gene encoding human DCIR was localized to chromosome 12p13, in a region close to the NK gene complex. Unlike members of this complex, DCIR displays a typical lectin CRD rather than an NK cell type extracellular domain, and was expressed on DC, monocytes, macrophages, B lymphocytes, and granulocytes, but not detected on NK and T cells. DCIR was strongly expressed by DC derived from blood monocytes cultured with GM-CSF and IL-4. DCIR was mostly expressed by monocyte-related rather than Langerhans cell related DC obtained from CD34+ progenitor cells. Finally, DCIR expression was down-regulated by signals inducing DC maturation such as CD40 ligand, LPS, or TNF-alpha. Thus, DCIR is differentially expressed on DC depending on their origin and stage of maturation/activation. DCIR represents a novel surface molecule expressed by Ag presenting cells, and of potential importance in regulation of DC function.
Bates
E E
EE
Laboratory for Immunological Research, Schering-Plough, Dardilly, France. elizabeth.bates@spcorp.com
Fournier
N
N
Garcia
E
E
Valladeau
J
J
Durand
I
I
Pin
J J
JJ
Zurawski
S M
SM
Patel
S
S
Abrams
J S
JS
Lebecque
S
S
Garrone
P
P
Saeland
S
S
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D002881:Chromosomes, Human, Pair 12; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000302:isolation & purification; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D018628:Gene Dosage; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D037181:Lectins, C-Type; D008099:Liver / Q000378:metabolism; D008221:Lymphoid Tissue / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000276:immunology; D009928:Organ Specificity / Q000235:genetics; D010446:Peptide Fragments / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D011971:Receptors, Immunologic; D011975:Receptors, Mitogen / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D014443:Tyrosine / Q000378:metabolism
C423004:CLEC4A protein, human; D018076:DNA, Complementary; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D011971:Receptors, Immunologic; D011975:Receptors, Mitogen; D014443:Tyrosine