Leukocytes have a heparan sulfate glycocalyx that regulates recruitment during inflammation

Abstract The glycocalyx is a proteoglycan-rich layer present on the surface of all mammalian cells that is particularly prevalent on endothelial cells lining the vasculature. It has been hypothesized that the glycocalyx mediates leukocyte migration by masking adhesion molecules and reducing leukocyte adhesion to the endothelium. Leukocyte recruitment is a key driver of inflammatory diseases, including the chronic skin disease, psoriasis. Here, we show that leukocytes express heparan sulfate, an important glycocalyx component, on their cell surface which is lost in response to psoriasis-like skin inflammation, whilst endothelial heparan sulfate expression is not affected. Treatment with a heparan sulfate mimetic during psoriasis-like skin inflammation protected heparan sulfate from cleavage by heparanase and resulted in reduced leukocyte accumulation in skin, yet unexpectedly, led to increased clinical signs of inflammation due to reduced Treg numbers. These findings change our understanding of immune cell recruitment by demonstrating the presence and function of a heparan sulfate glycocalyx on immune cells and urge caution on the use of heparanase inhibitors as therapies for inflammatory diseases. One Sentence SummaryLeukocytes express a glycocalyx on their surface which is shed in response to psoriasis-like skin inflammation, facilitating their migration into the skin.