An ultrasensitive and modular platform to detect Siglec ligands and control immune cell function

Area of Science:

• Immunology
• Glycobiology
• Biotechnology

Background:

• Siglecs (sialic acid-binding immunoglobulin-like lectins) are key regulators of immune cell function.
• Studying Siglec-ligand interactions is challenging due to the low affinity of Siglecs for their targets.
• Nature's use of multivalency inspired a new approach to overcome these limitations.

Purpose of the Study:

• To develop a multivalent platform for detecting Siglec glycan ligands.
• To profile Siglec ligands on human leukocytes and investigate Siglec-mediated immunomodulation.
• To assess the in vivo compatibility and applications of the developed platform.

Main Methods:

• Conjugation of recombinant Siglecs to liposomes using the SpyCatcher-SpyTag system to create Siglec-liposomes.
• Profiling of Siglec ligands on human leukocytes.
• In vivo studies demonstrating Siglec-liposome binding to brain vasculature.
• Investigation of Siglec-liposome effects on T cell proliferation.

Main Results:

• Siglec-liposomes provide a tunable and modular platform for presenting multiple Siglecs.
• New insights into Siglec ligands on human leukocytes were revealed.
• Siglec-7-liposomes demonstrated in vivo binding to brain vasculature in a mucin-dependent manner.
• Siglec-7-liposomes were found to increase T cell proliferation in a ST3Gal1-dependent and CD43-independent manner.

Conclusions:

• Siglec-liposomes are a versatile and sensitive tool for detecting Siglec glycan ligands.
• This platform offers new possibilities for studying Siglec-mediated immunomodulation.
• Siglec-liposomes have potential applications in both diagnostics and therapeutics.