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

  1. Shojiro Haji
  2. Taiki Ito
  3. Carla Guenther
  4. Miyako Nakano
  5. Takashi Shimizu
  6. Daiki Mori
  7. Yasunori Chiba
  8. Masato Tanaka
  9. Sushil K Mishra
  10. Janet A Willment
  11. Gordon D Brown
  12. Masamichi Nagae  Is a corresponding author
  13. Sho Yamasaki  Is a corresponding author
  1. Kyushu University, Japan
  2. Osaka University, Japan
  3. Hiroshima University, Japan
  4. Centre National de la Recherche Scientifique, France
  5. National Institute of Advanced Industrial Science and Technology, Japan
  6. Tokyo University of Pharmacy and Life Sciences, Japan
  7. University of Mississippi, United States
  8. 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.

The following data sets were generated

Article and author information

Author details

  1. Shojiro Haji

    Department of Molecular Immunology, Kyushu University, Fukuoka, Japan
    Competing interests
    The authors declare that no competing interests exist.
  2. Taiki Ito

    Laboratory of Molecular Immunology, Osaka University, Osaka, Japan
    Competing interests
    The authors declare that no competing interests exist.
  3. Carla Guenther

    Laboratory of Molecular Immunology, Osaka University, Osaka, Japan
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7915-1028
  4. Miyako Nakano

    Graduate School of Integrated Sciences for Life, Hiroshima University, Hiroshima, Japan
    Competing interests
    The authors declare that no competing interests exist.
  5. Takashi Shimizu

    Laboratory of Molecular Immunology, Osaka University, Osaka, Japan
    Competing interests
    The authors declare that no competing interests exist.
  6. Daiki Mori

    Centre National de la Recherche Scientifique, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Yasunori Chiba

    Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology, Ibaraki, Japan
    Competing interests
    The authors declare that no competing interests exist.
  8. Masato Tanaka

    Laboratory of Immune Regulation School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Japan
    Competing interests
    The authors declare that no competing interests exist.
  9. Sushil K Mishra

    Glycoscience Center of Research Excellence, University of Mississippi, Mississippi, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3080-9754
  10. Janet A Willment

    Medical Research Council Centre for Medical Mycology, University of Exeter, Exeter, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7040-0857
  11. Gordon D Brown

    Medical Research Council Centre for Medical Mycology, University of Exeter, Exeter, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  12. Masamichi Nagae

    Department of Molecular Immunology, Osaka University, Osaka, Japan
    For correspondence
    mnagae@biken.osaka-u.ac.jp
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5470-3807
  13. Sho Yamasaki

    Department of Molecular Immunology, Osaka University, Osaka, Japan
    For correspondence
    yamasaki@biken.osaka-u.ac.jp
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5184-6917

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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  1. Shojiro Haji
  2. Taiki Ito
  3. Carla Guenther
  4. Miyako Nakano
  5. Takashi Shimizu
  6. Daiki Mori
  7. Yasunori Chiba
  8. Masato Tanaka
  9. Sushil K Mishra
  10. Janet A Willment
  11. Gordon D Brown
  12. Masamichi Nagae
  13. Sho Yamasaki
(2022)
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

Share this article

https://doi.org/10.7554/eLife.83037

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