This study, co-authored by a research team that including researchers from Bio2Q and Keio University, identifies plant-derived glycolipids that can inhibit signaling through Mincle, an immune receptor involved in inflammatory responses.

While many previously identified Mincle ligands activate the receptor, relatively little is known about molecules that inhibit its signaling. Here, these researchers chemically synthesized a plant-derived disaccharide βASG found in yellow yam along with a series of related analogues and investigated their effects on Mincle activity. They found that several disaccharide βASGs strongly inhibited Mincle signaling while showing little ability to activate the receptor themselves. These compounds also suppressed signaling triggered by a glycolipid derived from Helicobacter pylori, which is associated with inflammatory responses in the stomach. By comparing different molecular structures, the researchers showed that the disaccharide framework together with sterol and fatty acid components plays an important role in determining inhibitory activity.

These findings reveal how structural changes to glycolipids can switch their effects on Mincle from activation to inhibition and provide a foundation for developing new molecules that regulate Mincle mediated immune responses.