Five mouse homologues of the human dendritic cell C-type lectin, DC-SIGN

Abstract

DC-SIGN, a human C-type lectin, is expressed on the surface of dendritic cells (DC), while a closely related human gene, DC-SIGNR or L-SIGN, is found on sinusoidal endothelial cells of liver and lymph node. Both DC-SIGN and DC-SIGNR/L-SIGN can bind ICAM-3 and HIV gp120, and transmit HIV to susceptible cells in trans. Here, we report the cloning of five mouse genes homologous to human DC-SIGN and DC-SIGNR/L-SIGN. Only one gene, named mouse DC-SIGN, is highly expressed in DC, and is not found in a panel of mouse macrophage and lymphocyte cell lines. The other four genes, named mouse SIGNR1 (SIGN-Related gene 1), SIGNR2, SIGNR3 and SIGNR4, are expressed at lower levels in various cells according to RT-PCR and Northern blot analyses on RNA. All the genes of mouse DC-SIGN and SIGNRs map to adjacent regions of chromosome 8 A1.2-1.3. However, like human DC-SIGN, only the mouse DC-SIGN gene is closely juxtaposed to the CD23 gene, while the other four SIGNR genes are located close to each other in a neighboring region. mRNAs of mouse DC-SIGN and three SIGNR genes encode type II transmembrane proteins (DC-SIGN, 238 amino acids; SIGNR1, 325 amino acids; SIGNR3, 237 amino acids; SIGNR4, 208 amino acids), but the SIGNR2 gene only encodes a carbohydrate recognition domain (CRD) without a cytosolic domain and a transmembrane domain (SIGNR2, 178 amino acids). Amino acid sequence similarities between the CRD of human DC-SIGN and the mouse homologues are 67% for DC-SIGN, 69% for SIGNR1, 65% for SIGNR2, 68% for SIGNR3 and 70% for SIGNR4 respectively. However, the membrane proximal neck domains in the mouse genes are much shorter than their counterparts in human DC-SIGN and DC-SIGNR/L-SIGN. This family of mouse C-type lectins is therefore complex, but only one of the new genes, DC-SIGN, is juxtaposed to CD23 and is expressed at high levels in DC.

C‐type lectin SIGNR1 enhances cellular oxidative burst response against C. albicans in cooperation with Dectin‐1

“…Thermal treatment of sSIGNR1 with Strep-Tactin at 371C enhanced binding activity. This result may be due to the aggregation of SIGNR1 via its long neck domain (116 amino acids), which contains a heptad-repeat sequence, leading to increased ligand affinity and specificity, as previously reported [22,25].…”

“…Thermal treatment of sSIGNR1 with Strep-Tactin at 371C enhanced binding activity. This result may be due to the aggregation of SIGNR1 via its long neck domain (116 amino acids), which contains a heptad-repeat sequence, leading to increased ligand affinity and specificity, as previously reported [22,25].Our study and several other reports indicate that Dectin-1 and TLR2 recognize microbial components and induce inflammatory responses in either a cooperative [15,29,30] or independent manner [13,14]. In RAW-control cells, zymosan induced weak oxidative burst, but TLR ligand-depleted zymosan and PAM 3 CSK 4 did not.…”

“…Mice have eight hDC-SIGN homologues [21,22]. One of these homologues, SIGNR1, has been shown to be expressed on particular Mf subsets in the marginal zone of the spleen, medulla of the lymph nodes and the peritoneal cavity [23][24][25] and to possess mannosebinding activities like hDC-SIGN.…”

“…HIV and HCV, have also found ways to subvert and use hDC-SIGN to their advantage [18,19]. Mycobacterium tuberculosis and HIV also target hDC-SIGN in order to upregulate DC production of the immunosuppressive cytokine IL-10 through Raf-1 kinase activation, which induces acetylation of the NF-kB p65 subunit in the presence of co-signaling from TLR4 [20].Mice have eight hDC-SIGN homologues [21,22]. One of these homologues, SIGNR1, has been shown to be expressed on particular Mf subsets in the marginal zone of the spleen, medulla of the lymph nodes and the peritoneal cavity [23][24][25] and to possess mannosebinding activities like hDC-SIGN.…”

Delivery of antigen using a novel mannosylated dendrimer potentiates immunogenicity in vitro and in vivo

“…Nevertheless, the affinity of MD to the C-type lectin DC-SIGN has been previously demonstrated [27]. DC-SIGN abundantly expressed in both human and mouse DC recognizes complex mannose residues and targets the late endolysosome [28][29][30].…”