Psoriasis & Immune Cells: How Sugars Drive Skin Inflammation – New Research
A newly discovered role for sugar molecules on immune cells is reshaping our understanding of psoriasis, a chronic inflammatory skin condition affecting millions worldwide. Researchers have found that these cells actively shed a sugar coating – a glycocalyx – to move from the bloodstream into the skin, challenging the long-held belief that changes primarily occurred within blood vessel walls. This finding, published in Science Signaling, could pave the way for more targeted therapies to control inflammation.
The study, led by Dr. Amy Saunders of Lancaster University and Dr. Douglas Dyer of the University of Manchester, with significant contributions from Dr. Megan Priestley (now at MIT), details how this process unfolds at a cellular level. Their work centers on a complex sugar molecule called heparan sulfate, a key component of the glycocalyx found on the surface of leukocytes – a type of white blood cell crucial to the immune response. The research reveals that these immune cells lose heparan sulfate as they migrate into inflamed skin, a process previously thought to be driven solely by changes in the surrounding blood vessels.
The Glycocalyx: More Than Just Protection
For years, the glycocalyx has been recognized for its protective functions. This dense outer layer, composed of complex sugar molecules, acts as a gel-like shield for cells, particularly those lining blood vessels, safeguarding them from physical stress and chemical damage. However, recent research has highlighted its role in regulating immune cell movement throughout the body. The team’s findings build on this understanding, demonstrating that the glycocalyx isn’t simply a passive bystander, but an active participant in the inflammatory process.
Previously, scientists theorized that alterations to the glycocalyx on blood vessel walls were the primary mechanism allowing immune cells to exit the bloodstream and enter tissues. This new study upends that notion, demonstrating that immune cells themselves possess a glycocalyx and actively modify it to facilitate their journey into inflamed areas. This shedding of the sugar coating appears to be a critical step in the body’s inflammatory response, enabling immune cells to reach sites of infection or injury. However, in conditions like psoriasis, this process becomes dysregulated, leading to an excessive accumulation of immune cells in the skin and persistent inflammation.
Psoriasis and the Immune Cell Sugar Shield
Psoriasis is an autoimmune disease characterized by raised, red, scaly patches on the skin. It’s a chronic condition with no cure, and current treatments primarily focus on managing symptoms. The disease affects an estimated 2-3% of the global population, according to the National Psoriasis Foundation, and can significantly impact quality of life. The new research offers a potential new angle for therapeutic intervention.
Dr. Saunders explained the significance of the discovery: “It is really exciting to discover how important the glycocalyx layer is on immune cells, and I hope that this research will support to lay the foundations for future advances in inflammatory disease treatment.” Dr. Dyer echoed this sentiment, stating, “It has been a pleasure working collaboratively on this project to redefine our understanding of immune cell recruitment to strive and better treat inflammatory disease.” Dr. Priestley added, “This was 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.”
Heparan Sulfate and the Role of Heparanase
The study delved deeper into the specific mechanisms at play, focusing on heparan sulfate. Researchers found that during psoriasis-like skin inflammation in mice, heparan sulfate was cleaved – broken down – from the surface of leukocytes. This cleavage was mediated by an enzyme called heparanase, produced by myeloid cells (another type of immune cell). Interestingly, the heparan sulfate on endothelial cells (cells lining blood vessels) remained unaffected.
When the researchers treated mice with a heparan sulfate mimetic – a molecule that resembles heparan sulfate – they were able to protect the heparan sulfate on leukocytes from being cleaved by heparanase. This resulted in reduced accumulation of immune cells in the skin. However, the results were complex. While leukocyte accumulation decreased, the clinical signs of inflammation actually increased. This unexpected finding suggests that heparan sulfate plays a more nuanced role than initially anticipated, potentially influencing the recruitment of regulatory T cells, which help to suppress inflammation.
Implications for Future Therapies and Ongoing Research
The findings underscore the importance of controlling immune cell movement in treating inflammatory diseases. By identifying the glycocalyx on immune cells as an active regulator of this process, the research opens up new avenues for drug development. Future therapies might focus on modulating the shedding of heparan sulfate, or targeting heparanase to prevent its breakdown. However, the complex interplay between heparan sulfate, immune cell recruitment, and inflammation – as evidenced by the unexpected increase in inflammation when heparan sulfate was protected – highlights the need for careful consideration and further investigation.
The study was primarily funded by The Wellcome Trust and the Royal Society, demonstrating the commitment of these organizations to advancing our understanding of inflammatory diseases. Further research is needed to fully elucidate the role of the glycocalyx in psoriasis and other inflammatory conditions, and to translate these findings into effective treatments. ScienceDaily reports that this discovery challenges previous assumptions about how immune cells navigate the body during inflammation.
What comes next involves refining our understanding of the complex effects of heparanase inhibitors on the immune response. Researchers will need to conduct further studies to determine the optimal strategies for modulating the glycocalyx and harnessing its potential for therapeutic benefit. Clinical trials will be essential to assess the safety and efficacy of any new therapies developed based on these findings. Ongoing surveillance of immune cell behavior and glycocalyx dynamics in patients with psoriasis will too be crucial for monitoring the effectiveness of existing treatments and identifying new targets for intervention.