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Blood, 15 June 2007, Vol. 109, No. 12, pp. 5337-5345.
Prepublished online as a Blood First Edition Paper on March 5, 2007; DOI 10.1182/blood-2006-09-048058.
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IMMUNOBIOLOGY
The DC-SIGNrelated lectin LSECtin mediates antigen capture and pathogen binding by human myeloid cells
Angeles Dominguez-Soto1,
Laura Aragoneses-Fenoll1,
Enrique Martin-Gayo2,
Lorena Martinez-Prats3,
Maria Colmenares1,
Marisa Naranjo-Gomez4,
Francesc E. Borras4,
Pilar Munoz5,
Mercedes Zubiaur5,
Maria L. Toribio2,
Rafael Delgado3, and
Angel L. Corbi1
1 Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), Madrid;
2 Centro de Biología Molecular "Severo Ochoa," Consejo Superior de Investigaciones Científicas, Madrid;
3 Hospital Doce de Octubre, Madrid;
4 Hospital Universitari Germans Trias i Pujol, Badalona;
5 Instituto de Parasitología y Biomedicina, Consejo Superior de Investigaciones Científicas, Granada, Spain
Liver and lymph node sinusoidal endothelial cell C-type lectin (LSECtin [CLEC4G]) is a C-type lectin encoded within the liver/lymph nodespecific intercellular adhesion molecule-3grabbing nonintegrin (L-SIGN)/dendritic cellspecific intercellular adhesion molecule-3grabbing nonintegrin (DC-SIGN)/CD23 gene cluster. LSECtin expression has been previously described as restricted to sinusoidal endothelial cells of the liver and lymph node. We now report LSECtin expression in human peripheral blood and thymic dendritic cells isolated ex vivo. LSECtin is also detected in monocyte-derived macrophages and dendritic cells at the RNA and protein level. In vitro, interleukin-4 (IL-4) induces the expression of 3 LSECtin alternatively spliced isoforms, including a potentially soluble form ( 2 isoform) and a shorter version of the prototypic molecule ( 3/4 isoform). LSECtin functions as a pathogen receptor, because its expression confers Ebola virusbinding capacity to leukemic cells. Sugar-binding studies indicate that LSECtin specifically recognizes N-acetyl-glucosamine, whereas no LSECtin binding to Mannan- or N-acetyl-galactosaminecontaining matrices are observed. Antibody or ligand-mediated engagement triggers a rapid internalization of LSECtin,which is dependent on tyrosine and diglutamic-containing motifs within the cytoplasmic tail. Therefore, LSECtin is a pathogen-associated molecular pattern receptor in human myeloid cells. In addition, our results suggest that LSECtin participates in antigen uptake and internalization, and might be a suitable target molecule in vaccination strategies.

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