{"id":"doi:10.1016/j.jbc.2023.105579","kind":"article","title":"The glycoimmune checkpoint receptor Siglec-7 interacts with T-cell ligands and regulates T-cell activation","authors":["Stewart N","Daly J","Drummond-Guy O","Krishnamoorthy V","Stark JC","Riley NM","Williams KC","Bertozzi CR","Wisnovsky S"],"author_count":9,"year":2024,"published":"2023-12-21","venue":"The Journal of biological chemistry","cited_by":38,"doi":"10.1016/j.jbc.2023.105579","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1016/j.jbc.2023.105579","archive_url":"https://space-kitty.com/papers/doi:10.1016/j.jbc.2023.105579","updated":null,"pmid":"38141764","pmcid":"PMC10831161","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC10831161/pdf","abstract":"Siglec-7 (sialic acid-binding immunoglobulin-like lectin 7) is a glycan-binding immune receptor that is emerging as a significant target of interest for cancer immunotherapy. The physiological ligands that bind Siglec-7, however, remain incompletely defined. In this study, we characterized the expression of Siglec-7 ligands on peripheral immune cell subsets and assessed whether Siglec-7 functionally regulates interactions between immune cells. We found that disialyl core 1 O-glycans are the major immune ligands for Siglec-7 and that these ligands are particularly highly expressed on naïve T-cells. Densely glycosylated sialomucins are the primary carriers of these glycans, in particular a glycoform of the cell-surface marker CD43. Biosynthesis of Siglec-7-binding glycans is dynamically controlled on different immune cell subsets through a genetic circuit involving the glycosyltransferase GCNT1. Siglec-7 blockade was found to increase activation of both primary T-cells and antigen-presenting dendritic cells in vitro, indicating that Siglec-7 binds T-cell glycans to regulate intraimmune signaling. Finally, we present evidence that Siglec-7 directly activates signaling pathways in T-cells, suggesting a new biological function for this receptor. These studies conclusively demonstrate the existence of a novel Siglec-7-mediated signaling axis that physiologically regulates T-cell activity. Going forward, our findings have significant implications for the design and implementation of therapies targeting immunoregulatory Siglec receptors.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"The glycoimmune checkpoint receptor Siglec-7 interacts with T-cell ligands and regulates T-cell activation\" by Stewart N, Daly J, Drummond-Guy O et al., https://doi.org/10.1016/j.jbc.2023.105579, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"synthetic-biology","name":"Synthetic Biology & Genome Engineering","domain_slug":"biotech"}],"cited_in_dossiers":[]}