title: Human C-type lectin domain family 4, member C (CLEC4C/BDCA-2/CD303) is a receptor for asialo-galactosyl-oligosaccharides.
abstract: Plasmacytoid dendritic cells are specialized in the production of type I interferon (type I IFN), which promotes antiviral and antitumor responses, as well as autoimmune disorders. Activation of type I IFN secretion depends on the pattern recognition receptors TLR7 and TLR9, which sense microbial RNA and DNA, respectively. Type I IFN production is modulated by several receptors, including the type II C-type lectin domain family 4, member C (CLEC4C). The natural ligand of CLEC4C is unknown. To identify it, here we probed a glycan array with a soluble form of the CLEC4C ectodomain. We found that CLEC4C recognizes complex type sugars with terminal galactose. Importantly, soluble CLEC4C bound peripheral blood leukocytes and tumor cells that express glycans with galactose residues at the non-reducing ends. The positive and negative modulation of galactose residues on cell membranes was paralleled by the regulation of type I IFN secretion by plasmacytoid dendritic cells in co-culture experiments in vitro. These results suggest that the modulation in the expression of non-sialylated oligosaccharides by invading pathogens or transformed cells may affect type I IFN response and immune surveillance.
authors: Dipartimento di Scienze Biomediche e Biotecnologie, Università degli Studi di Brescia, Viale Europa 11, 25123 Brescia, Italy.
authors: Elena
authors: E
authors: Riboldi
authors: Dipartimento di Scienze Biomediche e Biotecnologie, Università degli Studi di Brescia, Viale Europa 11, 25123 Brescia, Italy.
authors: Roberta
authors: R
authors: Daniele
authors: Dipartimento di Scienze Biomediche e Biotecnologie, Università degli Studi di Brescia, Viale Europa 11, 25123 Brescia, Italy.
authors: Carmen
authors: C
authors: Parola
authors: Istituto Clinico Humanitas IRCCS, Via Manzoni 113, 20089 Rozzano (MI), Italy.
authors: Antonio
authors: A
authors: Inforzato
authors: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110.
authors: Phoebe L
authors: PL
authors: Arnold
authors: Dipartimento di Scienze Biomediche e Biotecnologie, Università degli Studi di Brescia, Viale Europa 11, 25123 Brescia, Italy.
authors: Daniela
authors: D
authors: Bosisio
authors: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110.
authors: Daved H
authors: DH
authors: Fremont
authors: Istituto di Ricerche Farmacologiche "Mario Negri", via La Masa 19, 20156 Milano, Italy.
authors: Antonio
authors: A
authors: Bastone
authors: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110.
authors: Marco
authors: M
authors: Colonna
authors: Dipartimento di Scienze Biomediche e Biotecnologie, Università degli Studi di Brescia, Viale Europa 11, 25123 Brescia, Italy; Istituto Clinico Humanitas IRCCS, Via Manzoni 113, 20089 Rozzano (MI), Italy. Electronic address: sozzani@med.unibs.it.
authors: Silvano
authors: S
authors: Sozzani
mesh_terms: D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D016898:Interferon-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009844:Oligosaccharides / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011971:Receptors, Immunologic / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051199:Toll-Like Receptor 7 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: C443299:CLEC4C protein, human; D016898:Interferon-alpha; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D009844:Oligosaccharides; D011971:Receptors, Immunologic; C495348:TLR7 protein, human; C495371:TLR9 protein, human; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9