Leukocytes carry their own heparan sulfate sugar coat and shed it to exit the bloodstream into psoriatic skin, a 2025 Science Signaling paper shows — overturning the long-standing view that only blood-vessel walls drive this traffic.

The 18(911) paper, DOI 10.1126/scisignal.adr0011, reframes a step dermatologists have studied for two decades: how immune cells reach the dermis in chronic plaque psoriasis. Its title: "Leukocytes have a heparan sulfate glycocalyx that regulates recruitment during psoriasis-like skin inflammation."

What did the team actually measure?

The glycocalyx is a dense, gel-like layer of complex sugar molecules — including heparan sulfate chains — that coats many cell types, including the endothelium lining every blood vessel. For roughly 20 years, researchers have linked glycocalyx damage on vessel walls to leukocyte extravasation, the moment a circulating T cell or neutrophil squeezes out of the vasculature and into tissue.

In a mouse model of psoriasis-like inflammation, Saunders, Dyer, and colleagues tracked leukocytes as they crossed the vessel wall. The cells were not passive passengers. They actively remodeled their own sugar coat to enable egress.

That distinction matters because psoriasis is also a cellular-traffic problem: too many T cells, neutrophils, and dendritic cells arrive in the dermis and sustain plaques that itch, scale, and crack. Current biologics — IL-17, IL-23, and TNF inhibitors — blunt the signals those cells send after they arrive. They don't stop the arrival itself.

The endothelial glycocalyx also helps protect vessels from physical stress and chemical damage, which is why losing it carries consequences beyond leukocyte trafficking. The new work argues the leukocyte glycocalyx deserves the same mechanistic scrutiny in skin disease.

Who did the work?

Dr. Amy Saunders of Lancaster University co-led the project with Dr. Douglas Dyer of the University of Manchester. Their joint PhD student, Dr. Megan Priestley — now at MIT — leads the author list.

"It is really exciting to discover how important the glycocalyx layer is on immune cells," Saunders said, "and I hope that this research will help to lay the foundations for future advances in inflammatory disease treatment."

Priestley called it "a really fun project to work on in my PhD, and I hope this research brings more attention to the importance of sugars in the immune system."

Dyer added: "It has been a pleasure working collaboratively on this project to redefine our understanding of immune cell recruitment to try and better treat inflammatory disease."

Co-authors include Dr. Max Nobis at Manchester, previously at VIB-KU Leuven, and Professor Olga Zubkova at Victoria University of Wellington in New Zealand.

What does this change for psoriasis drug design?

If shedding the leukocyte glycocalyx is a rate-limiting step in skin recruitment, blocking that shedding — rather than only damping downstream cytokines — could blunt psoriatic flares at the front door. Pre-clinical candidates targeting heparan sulfate–processing enzymes have lagged IL-17 and IL-23 inhibitors in the clinic; the paper gives those programs a clearer mechanistic anchor.

The team frames the finding as a foundation for new drugs aimed at limiting harmful inflammation, not a therapeutic itself. Controlling how immune cells move between bloodstream and tissue remains a promising strategy across infectious and inflammatory disease, they note.

Funding came from the Wellcome Trust and the Royal Society. Watch for follow-up work in human psoriatic skin samples and, eventually, glycocalyx-stabilizing candidates in patients with moderate-to-severe disease.