An ultrasensitive and modular platform to detect Siglec ligands and control immune cell function
Siglecs are immunomodulatory receptors that regulate immune cell function. A fundamental challenge in studying Siglec-ligand interactions is the low affinity of Siglecs for their ligands. Inspired by how nature uses multivalency, we developed Siglec-liposomes as a highly multivalent and versatile platform for detecting Siglec glycan ligands in which recombinant Siglecs were conjugated to liposomes using the SpyCatcher-SpyTag system. Siglec-liposomes offer tunable multivalency and a modular assembly, enabling presentation of different Siglecs on the same liposome. Using Siglec-liposomes, we profiled Siglec ligands on human leukocytes, revealing distinct patterns of Siglec ligands. Moreover, Siglec-liposomes are in vivo compatible, where we demonstrated that Siglec-7-liposomes bind to the brain vasculature in a mucin domain-dependent manner. Given the abundance of Siglec ligands on T cells, we investigated whether Siglec-liposomes modulate T cell function and find that Siglec-7-liposomes increase T cell proliferation in an ST3Gal1-dependent and CD43-independent manner. Together, Siglec-liposomes are a versatile and sensitive tool for detecting Siglec ligands and immunomodulation.
Authors
- Sung-Yao Lin (ORCID: https://orcid.org/0009-0005-9252-0568)
- Megan K. Levings (ORCID: https://orcid.org/0000-0002-0305-5790)
- Jamey D. Marth (ORCID: https://orcid.org/0000-0001-9323-1649)
- Som G. Nanjappa (ORCID: https://orcid.org/0000-0001-8022-1353)
- Guilherme Meira Lima (ORCID: https://orcid.org/0000-0002-3268-6081)
- Stacy Alyse Malaker (ORCID: https://orcid.org/0000-0003-2382-5067)
- Sabine Ivison
- Maju Joe (ORCID: https://orcid.org/0000-0003-0664-5275)
- Jhon R. Enterina (ORCID: https://orcid.org/0000-0002-9137-3667)
- Ratmir Derda (ORCID: https://orcid.org/0000-0003-1365-6570)
- Edward N. Schmidt (ORCID: https://orcid.org/0000-0003-0729-5473)
- Reni John (ORCID: https://orcid.org/0009-0003-5932-1378)
- Madeline Crichton (ORCID: https://orcid.org/0009-0003-8783-7881)
- Liany Luna-Dulcey (ORCID: https://orcid.org/0000-0002-5931-4456)
- Fahima Mozaneh
- Matthew Scott Macauley (ORCID: https://orcid.org/0000-0003-4579-1048)
- Zeinab Jame-Chenarboo (ORCID: https://orcid.org/0009-0003-4687-8652)
- Kei Takahashi (ORCID: https://orcid.org/0000-0002-7925-6636)
- Jaesoo Jung (ORCID: https://orcid.org/0000-0002-9247-1066)
- Susmita Sarkar
- Chris D. St. Laurent (ORCID: https://orcid.org/0009-0007-9500-7406)
Institutions
- University of British Columbia (CA)
- University of Alberta (CA)
- University of Illinois Urbana-Champaign (US)
- Sanford Burnham Prebys Medical Discovery Institute (US)
- Discovery Institute (US)
- Yale University (US)
- BC Children's Hospital (CA)
Publication Details
- Journal
- Science Advances
- Published
- 2025-11-12
- DOI
- https://doi.org/10.1126/sciadv.adz8096
- Citations
- 1
- Primary Topic
- Biochemical and Structural Characterization
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- Children's Hospital Foundation
- BC Children's Hospital
- Alberta Innovates
- Canadian Institutes of Health Research
- Canadian Glycomics Network