Sugar coating on immune cells drives psoriasis inflammation

For decades, scientists studying psoriasis assumed they knew how the disease worked at the cellular level. Immune cells would leave the bloodstream and flood into inflamed skin, they believed, because the blood vessel walls themselves were changing—loosening their grip, so to speak, to let the invaders through. A new study from researchers at Lancaster University and the University of Manchester has upended that assumption. The problem, it turns out, lies not with the vessel walls but with the immune cells themselves. They are actively shedding a gel-like sugar coating that normally clings to their surface, and this shedding is what allows them to escape the bloodstream and enter the damaged skin below.

The sugar layer in question is called the glycocalyx. Nearly all cells in the body wear one—a dense, complex outer membrane made of sugar molecules that cling to the cell surface like a protective gel. On blood vessel walls, the glycocalyx serves obvious purposes: it shields the delicate inner lining from physical stress and chemical assault. But researchers have increasingly recognized that this coating does something else too. It acts as a kind of gatekeeper, controlling which cells can move where and when. The assumption, until now, was that the glycocalyx on blood vessels was the only player in the game. When immune cells needed to leave the bloodstream during an infection or inflammatory flare, the thinking went, the vessel walls would remodel their sugar coating to permit passage. The immune cells themselves were passive passengers in the process.

Dr. Megan Priestley, now at MIT, led the research as a joint PhD student under Dr. Amy Saunders and Dr. Douglas Dyer. What her team discovered was that immune cells are far from passive. They too have their own glycocalyx—their own sugar armor. And when the time comes to exit the bloodstream and enter inflamed tissue, they actively shed portions of this coating. The finding appeared in Science Signaling in a paper titled "Leukocytes have a heparan sulfate glycocalyx that regulates recruitment during psoriasis-like skin inflammation." The work involved collaborators including Dr. Max Nobis at the University of Manchester and Professor Olga Zubkova at Victoria University of Wellington in New Zealand.

The implications are significant because this shedding mechanism is a double-edged sword. In normal circumstances, when the body is fighting an infection, the ability of immune cells to strip away their sugar coating and slip out of the bloodstream is exactly what you want. It allows white blood cells to reach the site of danger and mount a defense. But in psoriasis, this same process goes haywire. Immune cells flood into the skin in excessive numbers, and their presence drives a cascade of inflammation that damages healthy tissue. The skin becomes red, thickened, and painful. Understanding that immune cells themselves control their own exit from the bloodstream opens a new angle of attack for drug designers. Rather than trying to modify blood vessel walls—a blunt instrument that could disrupt normal immune function—researchers might instead target the mechanism by which immune cells shed their glycocalyx. Slow or block that shedding, and fewer immune cells would make it into the inflamed skin.

Dr. Saunders reflected on the finding: "It is really exciting to discover how important the glycocalyx layer is on immune cells, and I hope that this research will help to lay the foundations for future advances in inflammatory disease treatment." Dr. Dyer added that the collaborative effort had been rewarding, noting that the work aimed to "redefine our understanding of immune cell recruitment to try and better treat inflammatory disease." Dr. Priestley, who conducted much of the research during her PhD, expressed hope that the work would draw greater attention to the role of sugars in immune function—a dimension of the system that has historically received less attention than proteins or genes.

The research was primarily funded by The Wellcome Trust and the Royal Society. The findings suggest that controlling immune cell movement between blood and tissue is a viable strategy not only for psoriasis but potentially for other inflammatory conditions where the immune system overshoots. The next phase will likely involve identifying which specific drugs or biological interventions can interfere with glycocalyx shedding without compromising the body's ability to fight genuine infections. That balance—between preventing harmful inflammation and preserving necessary immunity—will be the real test of whether this discovery translates into treatments that actually help patients.