Human Dectin-1 is O -glycosylated and serves as a ligand for C-type lectin receptor CLEC-2

• Published in: eLife 2022-12, Vol.11
• Main Authors: Haji, Shojiro, Ito, Taiki, Guenther, Carla, Nakano, Miyako, Shimizu, Takashi, Mori, Daiki, Chiba, Yasunori, Tanaka, Masato, Mishra, Sushil K, Willment, Janet A, Brown, Gordon D, Nagae, Masamichi, Yamasaki, Sho
• Format: Article
• Language: English
• Subjects: Animals; Antigens; Blood; Blood platelets; Blood Platelets - metabolism; Bone marrow; C-type lectin receptor; Experiments; Flow cytometry; Glycoconjugates; Glycosylation; Humans; Immune response; Immunology and Inflammation; Lectins, C-Type - metabolism; Lethality; Life Sciences; Ligands; Mice; Ontogeny; Pathogens; pattern recognition receptor; Peptides; Physiology; platelet
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.83037

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 -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.