Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan; Laboratory of Molecular Immunology, Immunology Frontier Research Center (IFReC), Osaka University, Osaka, Japan
Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan; Laboratory of Molecular Immunology, Immunology Frontier Research Center (IFReC), Osaka University, Osaka, Japan
Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan; Laboratory of Molecular Immunology, Immunology Frontier Research Center (IFReC), Osaka University, Osaka, Japan
Miyako Nakano
Graduate School of Integrated Sciences for Life, Hiroshima University, Hiroshima, Japan
Takashi Shimizu
Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan; Laboratory of Molecular Immunology, Immunology Frontier Research Center (IFReC), Osaka University, Osaka, Japan
Daiki Mori
Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan; Laboratory of Molecular Immunology, Immunology Frontier Research Center (IFReC), Osaka University, Osaka, Japan
Yasunori Chiba
Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan
Masato Tanaka
Laboratory of Immune Regulation School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Japan
Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan; Laboratory of Molecular Immunology, Immunology Frontier Research Center (IFReC), Osaka University, Osaka, Japan
Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan; Laboratory of Molecular Immunology, Immunology Frontier Research Center (IFReC), Osaka University, Osaka, Japan; Center for Infectious Disease Education and Research (CiDER), Osaka University, Osaka, Japan; Division of Molecular Design, Research Center for Systems Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
C-type lectin receptors (CLRs) elicit immune responses upon recognition of glycoconjugates present on pathogens and self-components. While Dectin-1 is the best-characterized CLR recognizing β-glucan on pathogens, the endogenous targets of Dectin-1 are not fully understood. Herein, we report that human Dectin-1 is a ligand for CLEC-2, another CLR expressed on platelets. Biochemical analyses revealed that Dectin-1 is a mucin-like protein as its stalk region is highly O-glycosylated. A sialylated core 1 glycan attached to the EDxxT motif of human Dectin-1, which is absent in mouse Dectin-1, provides a ligand moiety for CLEC-2. Strikingly, the expression of human Dectin-1 in mice rescued the lethality and lymphatic defect resulting from a deficiency of Podoplanin, a known CLEC-2 ligand. This finding is the first example of an innate immune receptor also functioning as a physiological ligand to regulate ontogeny upon glycosylation.
