Leukocytes have a heparan sulfate glycocalyx that regulates recruitment during psoriasis-like skin inflammation

Priestley, Megan and Hains, Anna and Mulholland, Iashia and Spijkers-Shaw, Sam and Müller, Joshua C. and Howell, Gareth and Ridley, Amanda J.L. and Davies-Strickleton, H. and Miller, Rebecca L. and Nobis, Max and Zubkova, Olga and Saunders, Amy and Dyer, Douglas (2025) Leukocytes have a heparan sulfate glycocalyx that regulates recruitment during psoriasis-like skin inflammation. Science Signaling, 18 (911). ISSN 1945-0877

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Abstract

The glycocalyx is a proteoglycan-rich layer present on the surface of all mammalian cells and is particularly prevalent on endothelial cells lining the vasculature. The glycocalyx is thought to affect leukocyte migration by masking adhesion molecules and reducing leukocyte adhesion to the endothelium. Leukocyte recruitment is a key driver of inflammatory diseases, including psoriasis. Here, we found that leukocytes had the glycocalyx component heparan sulfate on their cell surface and that it was lost in response to psoriasis-like skin inflammation. In contrast, endothelial heparan sulfate was not affected. Treatment with a heparan sulfate mimetic during psoriasis-like skin inflammation in mice protected heparan sulfate from cleavage by myeloid cell–derived heparanase and resulted in reduced leukocyte accumulation in the skin. However, clinical signs of inflammation were increased because of the reduced numbers of T regulatory cells that were recruited. These findings refine our understanding of immune cell recruitment by revealing the presence and function of a heparan sulfate glycocalyx on immune cells and highlight the complex effects of heparanase inhibitors on the immune response in this context.