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

Elife. 2022 Dec 8:11:e83037. 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 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.

Keywords: C-type lectin receptor; glycosylation; human; immunology; inflammation; mouse; pattern recognition receptor; platelet.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Platelets* / metabolism
  • Glycosylation
  • Humans
  • Lectins, C-Type* / metabolism
  • Ligands
  • Mice


  • dectin 1
  • Ligands
  • Lectins, C-Type
  • CLEC-2 protein, mouse

Associated data

  • GEO/GSE196049