title: 3-O-sulfo-β-D-galactose moiety of endogenous sulfoglycolipids is a potential ligand for immunoglobulin-like receptor LMIR5.
abstract: Axonal Guillain-Barré syndrome (GBS) is an autoimmune neuropathy characterized by limb weakness and/or paralysis due to the presence of autoantibodies against brain glycolipids. The immune receptors that recognize these autoimmune targets have not been described. In this study, 12 C-type lectin and 10 immunoglobulin-like receptors were screened for their potential ligands from the brain glycolipids, which are the binding targets for GBS autoantibodies. These glycolipids were GM1, GM2, GD1a, GD1b, GQ1b, crude gangliosides, and 3-O-sulfo-β-D-galactosylceramide C24:1 (designated as C24:1). A direct interaction between ligand and receptor was examined using an ELISA-based binding assay. C-type lectin (CLEC5a, SIGNR3) and immunoglobulin-like receptors (TREM2, TREM3, LMIR2, LMIR5, LMIR7, LMIR8) interacted with C24:1. In addition, TREM3 did bind to GQ1b. LMIR5 interacted with GD1a, GQ1b, and crude gangliosides. Binding with highest affinity was observed for the LMIR5-C24:1 interaction, which was selected for further verification. C24:1 was found to induce MCP-1 production, but not proinflammatory cytokines, in basophils. C24:1-induced MCP-1 production was significantly reduced in DAP12(-/-) basophils. Importantly, LMIR5 ligation by C24:1 resulted in NFAT activation through DAP12 in LMIR5-expressing reporter cells. Structural analysis showed that LMIR5 recognized the 3-O-sulfo-β-D-galactose moiety of C24:1. The findings indicated that C24:1 is a potential ligand for DAP12-coupled LMIR5.
authors.affiliation: Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan. Electronic address: vongsavanh@bioreg.kyushu-u.ac.jp.
authors.forename: Vongsavanh
authors.initials: V
authors.lastname: Phongsisay
authors.affiliation: Division of Molecular and Cellular Immunoscience, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Japan.
authors.forename: Ei'ichi
authors.initials: E
authors.lastname: Iizasa
authors.affiliation: Division of Molecular and Cellular Immunoscience, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Hara
authors.affiliation: Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Yamasaki
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D001491:Basophils / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D018932:Chemokine CCL2 / Q000096:biosynthesis; D005690:Galactose / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism*; D006017:Glycolipids / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008810:Mice, Inbred C57BL; D011971:Receptors, Immunologic / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018932:Chemokine CCL2; D006017:Glycolipids; D008024:Ligands; D011971:Receptors, Immunologic; C484963:Tyrobp protein, mouse; C011117:sulfoglycolipids; C078458:3-O-sulfogalactose; D005690:Galactose
keywords: Brain glycolipids; LMIR5/CD300b; Ligand