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.
-
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.
Metrics
-
- 1,368
- views
-
- 251
- downloads
-
- 6
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
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
Further reading
-
- Immunology and Inflammation
The adaptive T cell response is accompanied by continuous rewiring of the T cell’s electric and metabolic state. Ion channels and nutrient transporters integrate bioelectric and biochemical signals from the environment, setting cellular electric and metabolic states. Divergent electric and metabolic states contribute to T cell immunity or tolerance. Here, we report in mice that neuritin (Nrn1) contributes to tolerance development by modulating regulatory and effector T cell function. Nrn1 expression in regulatory T cells promotes its expansion and suppression function, while expression in the T effector cell dampens its inflammatory response. Nrn1 deficiency in mice causes dysregulation of ion channel and nutrient transporter expression in Treg and effector T cells, resulting in divergent metabolic outcomes and impacting autoimmune disease progression and recovery. These findings identify a novel immune function of the neurotrophic factor Nrn1 in regulating the T cell metabolic state in a cell context-dependent manner and modulating the outcome of an immune response.
-
- Immunology and Inflammation
Antibodies are powerful tools for the therapy and diagnosis of various diseases. In addition to conventional hybridoma-based screening, recombinant antibody-based screening has become a common choice; however, its application is hampered by two factors: (1) screening starts after Ig gene cloning and recombinant antibody production only, and (2) the antibody is composed of paired chains, heavy and light, commonly expressed by two independent expression vectors. Here, we introduce a method for the rapid screening of recombinant monoclonal antibodies by establishing a Golden Gate-based dual-expression vector and in-vivo expression of membrane-bound antibodies. Using this system, we demonstrate the rapid isolation of influenza cross-reactive antibodies with high affinity from immunized mice within 7 days. This system is particularly useful for isolating therapeutic or diagnostic antibodies, for example during foreseen pandemics.
