What is it about?

The surface of human cells is covered by a dense layer of sugar molecules that regulates interactions with the immune system, bacteria and viruses. This sugar layer is composed of many different types of sugars that are linked to each other in complex structures called glycans. One of these sugars is sialic acid and it can be recognized by Siglec receptors that have important functions in the the immune system and beyond. In this study, we have created a large library of genetically engineered cells containing different sialic acid sugars on their surface. With this library, the cell-based sialic acid array, we have studied how Siglec receptors bind to and interact with sialic acids.

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Why is it important?

We have established how the sugars bind to and activate the the Siglec receptors that regulate immunity. These receptors play a major role, as they tell the immune system to decrease or increase activities which is important to fight infections, but also to dampen the immune response to avoid autoimmunity. Furthermore, we have identified sialic acid ligands for the Siglec-3 receptor. Mutations in the Siglec-3 receptor are already known to play a role in connection with Alzheimer’s, but it was unknown to what the receptor specifically binds. In this study, we have identified a potential natural sialic acid sugar that binds specifically to the Siglec-3 receptor. This knowledge represents an important step forwards in understanding the genetic defects that cause a person to develop the disease.


The obtained insight into how Siglecs receptors recognize sialic acids and which ones enables further studies into the role that these receptors play in immune recognition, infection and autoimmunity. Our findings provide new leads for the development of sialic acid sugars for targeting of Siglecs in a therapeutic setting, for example to reduce immune activation in inflammation and autoimmunity. Moreover, the discovery of a defined glycan ligand for Siglec-3 now opens up for studies into the function of this receptor in brain physiology and Alzheimer’s disease.

Christian Bull
Copenhagen University

Read the Original

This page is a summary of: Probing the binding specificities of human Siglecs by cell-based glycan arrays, Proceedings of the National Academy of Sciences, April 2021, Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.2026102118.
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