Understanding Psoriasis: A Chronic Skin Condition Affecting Millions

Psoriasis is a common, long-lasting autoimmune disease characterized by rapid skin cell growth, leading to thick, scaly patches on the skin's surface. These patches, often red with silvery-white scales, typically appear on elbows, knees, scalp, and lower back, but can affect any area, including nails and joints in more severe cases like psoriatic arthritis. The condition arises when the immune system mistakenly attacks healthy skin cells, triggering inflammation and excessive cell turnover—normal skin cells renew every 28-30 days, but in psoriasis, this happens in just 3-4 days.

Worldwide, psoriasis impacts approximately 125 million people, representing 2-3% of the global population. In the United States alone, over 8 million individuals live with the disease. While not life-threatening, it significantly reduces quality of life, causing itching, burning, pain, and emotional distress like anxiety and depression. Triggers include stress, infections, cold weather, and certain medications, but genetics play a major role—those with a family history are at higher risk.

Current treatments range from topical creams (corticosteroids, vitamin D analogs) for mild cases to phototherapy and systemic medications like methotrexate for moderate to severe. Biologics targeting specific immune pathways, such as tumor necrosis factor (TNF) inhibitors, interleukin-17 (IL-17) blockers, and IL-23 inhibitors, have revolutionized care, achieving clear or almost clear skin in up to 90% of patients. However, not everyone responds, side effects exist, and there's no cure, prompting ongoing research into novel mechanisms.

🔬 The Groundbreaking Discovery: A Concealed Sugar Layer on Immune Cells

In late 2025, researchers unveiled a surprising mechanism fueling psoriasis inflammation: a hidden sugar layer, or glycocalyx, on immune cells themselves. Previously overlooked, this gel-like coating of sugar molecules—specifically heparan sulfate (HS) glycans—covers leukocytes like monocytes and regulates their migration into the skin. During psoriasis flare-ups, these cells shed the layer, enabling aggressive infiltration that perpetuates the cycle of inflammation.

Led by Dr. Amy Saunders at Lancaster University and Dr. Douglas Dyer at the University of Manchester, with first author Dr. Megan Priestley (now at MIT), the study challenged the long-held view that only blood vessel linings (endothelium) adjust their glycocalyx to permit immune entry. Published in Science Signaling on November 4, 2025 (read the full paper), the findings open doors to glycan-targeted therapies.

What is the Glycocalyx? Decoding the Sugar Shield on Cells

Every human cell is enveloped by a glycocalyx—a dynamic, carbohydrate-rich layer protruding from the cell membrane like a fuzzy coat. Composed of glycoproteins, glycolipids, and proteoglycans like heparan sulfate, it acts as a protective barrier against shear stress in blood flow, mechanical damage, and unwanted interactions. In glycobiology (the study of sugar molecules in biology), glycans are short chains of sugars attached to proteins or lipids, forming complex structures that influence cell signaling, adhesion, and recognition.

Heparan sulfate, a key glycan, is a long, unbranched polysaccharide resembling heparin (an anticoagulant). It binds chemokines, growth factors, and adhesion molecules, modulating their activity. On endothelial cells lining blood vessels, the glycocalyx repels circulating immune cells under normal conditions. During infection or injury, enzymes like heparanase trim it, exposing adhesion sites for immune cells to roll, stick, and squeeze through (extravasation).

• Structure: 50-100 nm thick, hydrated gel with negative charge from sulfate groups.
• Functions: Mechanoprotection, anti-thrombosis, immune modulation.
• Dynamics: Constantly remodeled by synthases (add sugars) and hydrolases (shed them).

This sugar shield was known on endothelium, but the new research proves leukocytes have their own HS glycocalyx, shedding it actively in response to inflammation signals.

From Rolling to Invasion: The Journey of Immune Cells in Inflammation

Immune cell recruitment follows a precise cascade:

1. Tethering/Rolling: Selectins on endothelium bind sialylated glycans on leukocytes, slowing them in blood flow.
2. Activation: Chemokines (e.g., CCL7 in psoriasis) trigger integrin activation on leukocytes.
3. Firm Adhesion: Integrins (LFA-1) bind ICAM-1/VCAM-1 on endothelium.
4. Extravasation: Leukocytes crawl, form transendothelial projections, and migrate into tissue.

Prior models emphasized endothelial glycocalyx shedding via heparanase from immune cells. The discovery flips this: leukocytes shed their own HS glycocalyx first, reducing electrostatic repulsion and enhancing adhesion.

Experimental Evidence: Unmasking the Mechanism in Psoriasis Models

Using an imiquimod (IMQ)-induced mouse model mimicking human psoriasis—with ear thickening, scaling, and immune infiltration—the team stained leukocytes for HS. Migrated monocytes showed significantly reduced surface HS, confirmed by flow cytometry after 2-hour chemotaxis assays toward CCL7.

Myeloid cells released heparanase, cleaving leukocyte HS. Treating with HS mimetics (fondaparinux) protected the glycocalyx, curbing infiltration but paradoxically worsening inflammation by hindering regulatory T cells (Tregs), which suppress overreactions.

Findings align with human psoriasis, where similar chemokine gradients and heparanase upregulation occur. Dr. Saunders noted, "It is really exciting to discover how important the glycocalyx layer is on immune cells."

📈 Implications for Psoriasis Treatment: Targeting Glycans for Precision Therapy

This revelation suggests therapies modulating leukocyte glycocalyx:

• Heparanase Inhibitors: Already in cancer trials (e.g., pixatimod), could limit shedding but risk Treg imbalance.
• Glycan Mimetics: Synthetic HS to stabilize the layer, fine-tuning recruitment.
• Glycoengineering: Editing leukocyte glycosylation via CRISPR for autoimmune control.

Unlike broad immunosuppressants, glycan targets offer specificity, potentially fewer infections. Combined with existing biologics, they could achieve sustained remission. For patients, this means hope for flare prevention amid a pipeline boasting TYK2 inhibitors (deucravacitinib), IL-23 blockers (icotrokinra), and next-gen IL-17 agents.

Explore research jobs in immunology or higher education positions in dermatology to contribute to these advances.

Broader Impacts: Revolutionizing Inflammatory Disease Management

Beyond psoriasis, glycocalyx dysregulation drives rheumatoid arthritis, inflammatory bowel disease, and atherosclerosis. In infections, enhancing shedding aids pathogen clearance; in autoimmunity, inhibiting it curbs damage. This dual role demands nuanced drugs—context-specific activation.

Funding from Wellcome Trust and Royal Society underscores glycobiology's rise. Collaborations like Lancaster-Manchester highlight interdisciplinary potential in biomedical sciences.

Learn more via the Lancaster University press release or National Psoriasis Foundation stats.

Future Directions: From Bench to Bedside in Glycobiology Research

Ongoing work includes human biopsies for HS profiling, intravital imaging of shedding in vivo, and nanoparticle-delivered glycan modulators. Clinical trials could test heparanase blockers in psoriasis within 5 years.

For academics, this sparks opportunities in glycoengineering and immune trafficking. Check tips for academic CVs or postdoc roles in related fields.

Photo by Logan Voss on Unsplash

Wrapping Up: A Sweeter Path Forward for Psoriasis Patients

The hidden sugar layer discovery reframes psoriasis as a glycan-orchestrated disorder, promising targeted interventions. Stay informed, advocate for research funding, and share experiences on Rate My Professor or explore higher ed jobs in health sciences. With innovations like this, clearer skin—and lives—are on the horizon.