In a groundbreaking study that redefines our understanding of immune cell dynamics during inflammatory skin disease, researchers have unveiled new insights into how glycans—complex sugar molecules—regulate leukocyte recruitment in psoriasis. Published in the prestigious journal Science Signaling, this research, led by Dr. Amy Saunders of Lancaster University and Dr. Douglas Dyer from the University of Manchester, challenges previous paradigms by highlighting the critical role of the immune cells’ own glycocalyx in navigating tissue infiltration.
The glycocalyx, a dense and intricate sugar-rich layer enveloping the surface of many cells, including those lining blood vessels, has traditionally been studied in the context of vascular biology. This gel-like extracellular matrix has been well established as a protector against mechanical stress and chemical insults, maintaining vascular integrity. However, its role in immune cell trafficking, particularly during pathological inflammation, has been less understood. Newcastle data from this study show that leukocytes themselves possess a heparan sulfate-rich glycocalyx, a feature previously underestimated in immune cell migration.
The investigation into psoriasis-like skin inflammation—a chronic autoimmune condition known for its debilitating inflammatory cascades—revealed that leukocytes actively shed their glycocalyx to facilitate transmigration from blood vessels into affected tissues. This finding contradicts the longstanding dogma that only endothelial cells modulate their glycocalyx to permit immune cell extravasation. Instead, it unveils a bidirectional, dynamic remodeling, with both vascular and immune cell surfaces adapting during inflammatory responses.
Mechanistically, the shedding of the heparan sulfate glycocalyx on leukocytes lowers the physical and biochemical barriers preventing their movement, effectively easing their passage through the endothelium. This process appears to be a finely tuned immune strategy, enabling rapid tissue infiltration when defense against infection is needed. Yet, in conditions like psoriasis, this same mechanism inadvertently fuels chronic inflammation, leading to persistent tissue damage and disease progression.
The intricate balance of glycocalyx synthesis and shedding on leukocytes reflects a sophisticated modulation of cellular adhesion molecules and chemokine receptor signaling. Alterations in this sugar coating influence integrin activation and receptor clustering, thereby modulating the avidity and affinity of immune cells for the vascular endothelium. These cellular sugar moieties act like molecular switches that regulate the trafficking of immune cells, a concept that opens exciting therapeutic opportunities.
This research team employed cutting-edge experimental techniques including enzymatic digestion assays, flow cytometry, and in vivo imaging to elucidate the role of glycocalyx remodeling. Their meticulous approach allowed them to map the dynamic changes in glycocalyx composition on leukocytes under inflammatory conditions, correlating these changes with enhanced migratory capacity in skin tissues affected by psoriasis.
Dr. Amy Saunders expressed enthusiasm for the discovery, emphasizing how the study lays critical groundwork for future research aimed at targeting glycocalyx dynamics therapeutically. She highlighted that modulating leukocyte glycocalyx shedding could serve as a novel intervention point to prevent excessive immune cell infiltration characteristic of autoimmune and inflammatory skin diseases, potentially revolutionizing patient outcomes.
Similarly, Dr. Douglas Dyer underscored the collaborative effort behind this discovery, noting how redefining immune cell recruitment mechanisms offers promising avenues to refine treatments not only for psoriasis but possibly other inflammatory disorders where immune cell migration is dysregulated. The implications extend into designing drugs that can precisely intervene in glycocalyx remodeling pathways, offering specificity with potentially fewer side effects.
First author Dr. Megan Priestley, now continuing her research career at MIT, reflected on the excitement of exploring the role of sugars in immune modulation. Her work highlights the often-overlooked significance of glycans beyond their structural functions, positioning them as critical immunological regulators that merit further exploration in disease contexts.
Additional collaborators, including Dr. Max Nobis and Professor Olga Zubkova, contributed expertise that enriched the study’s multidisciplinary approach. Their combined efforts have produced a comprehensive picture of how leukocyte glycocalyx remodeling is not merely a biochemical curiosity but a fundamental physiological process in immune surveillance and pathology.
Ultimately, the study points toward a paradigm shift in understanding leukocyte recruitment during inflammation. The glycocalyx, once seen primarily as a vascular protector, is now recognized as a dynamic immune cell surface regulator vital in both health and disease. This insight paves the way for innovative therapeutic strategies that could manipulate this sugar layer to control immune cell movement, balancing protection against pathogens with the prevention of autoimmunity.
The research received key funding from The Wellcome Trust and the Royal Society, reflecting its importance and potential impact in the biomedical field. As immunology and glycoscience continue to intersect, findings like these illuminate complex cellular interactions that underpin disease and health, heralding a new era of precision medicine centered on glycocalyx biology.
Subject of Research: People
Article Title: Leukocytes have a heparan sulfate glycocalyx that regulates recruitment during psoriasis-like skin inflammation
News Publication Date: 4-Nov-2025
Web References: http://dx.doi.org/10.1101/2024.05.21.595098
Image Credits: Lancaster University
Keywords: Inflammatory disorders, Arthritis, Encephalitis, Meningitis, Immune disorders, Nephritis, Peritonitis, Cells, Immunology, Leukocytes, Immune cells, Public health, Persistent infections, Autoimmune disorders, Skin disorders, Psoriasis
