Human Dectin-1 is O-glycosylated and serves as a ligand for C-type lectin receptor CLEC-2
- Kyushu University, Japan
- Osaka University, Japan
- Hiroshima University, Japan
- Centre National de la Recherche Scientifique, France
- National Institute of Advanced Industrial Science and Technology, Japan
- Tokyo University of Pharmacy and Life Sciences, Japan
- University of Mississippi, United States
- University of Exeter, United Kingdom
Abstract
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 b-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.
Data availability
Sequencing data have been deposited in GEO under accession code GSE196049.
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RNA sequencing of human monocytes stimulated with murine platelets from wild-type or Clec1b-/- miceNCBI Gene Expression Omnibus, GSE196049.
Article and author information
Author details
Funding
Japan Society for the Promotion of Science (20H00505)
- Sho Yamasaki
Japan Society for the Promotion of Science (20K06575)
- Masamichi Nagae
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal protocols were approved by the committee of Ethics on Animal Experiment and Research Institute for Microbial Diseases, Osaka University (Permit number: Biken-AP-R03-17-0).
Human subjects: All human subjects research was approved by the Institutional Review Board of the Research Institute for Microbial Diseases, Osaka University. Informed consent and consent to publish were obtained from all individuals donating venous blood. Consent documents and procedures were approved by the Institutional Review Board of the Research Institute for Microbial Diseases, Osaka University (Permit number 29-12).
Copyright
© 2022, Haji et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Human Dectin-1 is O-glycosylated and serves as a ligand for C-type lectin receptor CLEC-2
eLife 11:e83037.
https://doi.org/10.7554/eLife.83037
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