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

Area of Science:

• Immunology
• Glycobiology
• Biotechnology

Background:

• Siglecs are key immunomodulatory receptors regulating immune cell function.
• Low affinity of Siglec-ligand interactions presents a challenge for studying these interactions.
• Nature's use of multivalency inspired a new approach to Siglec research.

Purpose of the Study:

• To develop a versatile and sensitive platform for detecting Siglec glycan ligands.
• To investigate Siglec ligand patterns on human leukocytes.
• To explore the in vivo compatibility and immunomodulatory potential of Siglec-liposomes.

Main Methods:

• Conjugation of recombinant Siglecs to liposomes using the SpyCatcher-SpyTag system to create Siglec-liposomes.
• Profiling Siglec ligands on human leukocytes using the Siglec-liposome platform.
• Assessing in vivo binding of Siglec-7-liposomes to brain vasculature.
• Investigating the effect of Siglec-7-liposomes on T cell proliferation.

Main Results:

• Siglec-liposomes demonstrated tunable multivalency and modular assembly.
• Distinct patterns of Siglec ligands were identified on human leukocytes.
• Siglec-7-liposomes showed in vivo compatibility, binding to brain vasculature in a mucin domain-dependent manner.
• Siglec-7-liposomes were found to increase T cell proliferation in an ST3Gal1-dependent and CD43-independent manner.

Conclusions:

• Siglec-liposomes represent a versatile and sensitive tool for detecting Siglec glycan ligands.
• This platform facilitates the study of Siglec-ligand interactions and their role in immune cell function.
• Siglec-liposomes hold potential for immunomodulation and therapeutic applications.