High impact information on CLEC7A

• (2005) in this issue of Immunity, that ligand binding by the C type lectin Dectin-1 leads to recruitment of the tyrosine kinase Syk and is critical to subsequent cytokine production by the cell, will surely inspire further research on the mechanisms of carbohydrate receptor signaling [1].
• Our results establish a fundamental function for beta-glucan recognition by dectin-1 in antifungal immunity and demonstrate a signaling non-Toll-like pattern-recognition receptor required for the induction of protective immune responses [2].
• Dectin-1-deficient leukocytes demonstrated significantly impaired responses to fungi even in the presence of opsonins [2].
• Residual cytokine production was mediated by recognition of beta-glucan by the dectin-1/TLR2 receptor complex [3].
• Production of proinflammatory TNFalpha by phagocytes was suppressed either by the presence of the alpha-(1,3)-glucan layer on yeast cells or by RNA interference based depletion of the host beta-glucan receptor dectin-1 [4].

Biological context of CLEC7A

• The DECTIN-1 gene was localized in the natural killer gene complex on human Chromosome 12p12.3-p13.2, between OLR1 and CD94 (position 21.8 cM on the genetic map) [5].
• DECTIN-1 gene maps to chromosome 12, between p13.2 and p12.3, close to the NK gene complex (12p13.1 to p13.2) which contains genes for NK lectin receptors [6].
• CONCLUSION: The Dectin-1 gene is expressed during the development of DC from peripheral blood monocytes and the transfection of the splice variant 1b into HeLa cells results in the stimulation of effector functions of human T lymphocytes [7].
• Dectin-1 is a C-type lectin-like receptor on leukocytes that mediates phagocytosis and inflammatory mediator production in innate immunity to fungal pathogens [8].
• Microbial carbohydrate structures are recognized by pathogen associated molecular pattern (PAMP) receptors of innate immunity including C-type lectins such as MBL, the tandem-repeat-type macrophage mannose receptor, DC-SIGN or dectin-1 of dendritic cells, certain TLRS or the TCR of NKT cells [9].

Anatomical context of CLEC7A

• DECTIN-1 is selectively expressed in dendritic cells and to a lower extent in monocytes and macrophages. mRNA forms with and without a stalk exon are observed [10].
• During functional maturation of dendritic cells the level of DECTIN-1 mRNA is down-regulated several-fold [10].
• DC-SIGN and Dectin-1 were also expressed in COS cells to compare their ability to trigger particle internalization in a nonphagocytic cell line [11].
• In addition to its exogenous ligands, Dectin-1 can recognize an unidentified endogenous ligand on T cells and may act as a co-stimulatory molecule, although its function in these responses is less clear [12].
• Dectin-1 is expressed on phagocytic cells, including macrophages and neutrophils, and mediates both the internalization and cellular responses to beta-glucan, through unique mechanisms [12].

Associations of CLEC7A with chemical compounds

• We identified a new Ca2+-dependent lectin-like receptor gene, DECTIN-1 (HGMW-approved symbol CLECSF12), the human orthologue of mouse Dectin-1, coding for a putative type II transmembrane glycoprotein with an extracellular C-type lectin-like domain [5].
• Among these, Dectin-1 binding is detected exclusively to 1,3-linked glucose oligomers, the minimum length required for detectable binding being a 10- or 11-mer [8].
• We have investigated this, since Dectin-1 shows glucan-independent binding to a subset of T-lymphocytes and is involved in triggering their proliferation [8].
• Forming Ft phagosomes accumulated MR, and infection was inhibited by MR-blocking antibody or soluble mannan but not by the dectin-1 ligand laminarin [13].

Physical interactions of CLEC7A

• Human Dectin-1 isoform E is a cytoplasmic protein and interacts with RanBPM [14].

Other interactions of CLEC7A

• Whereas recombinant full-length DECTIN-1 and LOX-1 are transported to the cell surface, CLEC-1 proteins accumulate in perinuclear compartments [10].
• Moreover, an association of CD63 with the beta-glycan receptor dectin-1 was observed [15].
• Moreover, as binding of zymosan particles to the PMNs' surface remained unchanged despite increasingly suppressed phagocytosis and associated H2O2 production, observed effects are likely to reflect defects in signaling by the lectin-binding site of CD11b and/or the beta-glucan receptor dectin-1, respectively [16].
• Because cytokine secretion by DCs has recently been shown to be regulated by Fas ligand (FasL), its role in beta-glucan activation of DCs was also investigated. beta-Glucan-induced DC activation occurred in part through dectin-1 receptors [17].
• Among them, one should mention the DC-specific ICAM-3-grabbing nonintegrin, the mannose receptor, Dectin-1 (the major beta-glucan receptor) and NOD2 [18].

Analytical, diagnostic and therapeutic context of CLEC7A

• In addition, expression of the beta-glucan receptor dectin-1 was shown in eosinophils by reverse transcriptase-polymerase chain reaction [19].
• Inflammatory cells, recruited in vivo using a new skin-window technique, demonstrated that Dectin-1 expression was not significantly modulated on macrophages during inflammation, but is decreased on recruited granulocytes [20].
• To identify the human homologue (DECTIN-1), we employed degenerative PCR amplification of mRNA isolated from DC and subsequent cDNA cloning [6].
• Dectin-1 lacks residues involved in calcium ligation that mediates carbohydrate-binding by classical C-type lectins; nevertheless, it binds zymosan, a particulate beta-glucan-rich extract of Saccharomyces cerevisiae, and binding is inhibited by polysaccharides rich in beta1,3- or both beta1,3- and beta1,6-linked glucose [8].
• Dectin-1 mRNA was detected predominantly in spleen and thymus (by Northern blotting) and in skin-resident DC, i.e. Langerhans cells (by reverse transcription-polymerase chain reaction) [21].

References