# The glycoimmune checkpoint receptor Siglec-7 interacts with T-cell ligands and regulates T-cell activation

Article · Stewart N, Daly J, Drummond-Guy O, Krishnamoorthy V, Stark JC, Riley NM, Williams KC, Bertozzi CR, Wisnovsky S

- Archive id: doi:10.1016/j.jbc.2023.105579
- Published: 2023-12-21
- Venue: The Journal of biological chemistry
- DOI: https://doi.org/10.1016/j.jbc.2023.105579
- PMID: 38141764
- PMCID: PMC10831161
- Citations: 38
- Source URL: https://doi.org/10.1016/j.jbc.2023.105579
- PDF: https://europepmc.org/articles/PMC10831161/pdf
- Provenance: europepmc

## 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 reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Synthetic Biology & Genome Engineering](https://space-kitty.com/topics/synthetic-biology)

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