Understanding Why Psoriasis Itches
Psoriasis is a long-term skin disease that affects about 3% of people worldwide. It causes red, scaly patches on the skin, but one of the most difficult symptoms for many patients is constant itching. Up to 90% of people with psoriasis experience ongoing itch, which can disrupt sleep, affect mental health, and greatly reduce quality of life. At the Granville Lab at the International Collaboration on Repair Discoveries (ICORD), we are working to better understand why this itch happens and how we might develop treatments to relieve it.
Recent research suggests that a group of proteins called granzymes may play an important role in psoriasis. Granzymes are enzymes made by immune cells and skin cells. They act like tiny scissors that cut other proteins in the body. Cutting a protein can have different effects: it can stop the protein from working, change what it does, or even activate it. Because of this, granzymes can influence many processes in the body, including inflammation and how skin cells grow.
One granzyme, called granzyme K (GzmK), is found at high levels in the skin of people with psoriasis. GzmK can break down proteins that help keep the skin healthy, which worsens skin damage and inflammation. Our lab has also found that GzmK causes skin cells to grow too quickly, leading to the thickened skin that is typical of psoriasis. Since GzmK can cut many different proteins, it may affect a wide range of skin functions. In addition to these effects, we believe GzmK may also play a role in causing the sensation of itch in psoriasis.
We think that GzmK not only damages the skin but also activates nearby nerve cells that send itch signals to the brain. Nerve cells in the skin are responsible for sensing itch. When the skin becomes inflamed and damaged, these nerves can become overly sensitive, like exposed wires that constantly send signals. Proteins such as GzmK may trigger these nerves to send continuous itch signals to the brain, creating the strong urge to scratch. In fact, previous studies have shown that mice injected with GzmK scratch more than normal. Other experiments have shown that sensory nerve cells grown in the presence of GzmK become overactive.
The first goal of my research is to study how GzmK contributes to itch using a mouse model of psoriasis. To do this, we use a cream called imiquimod, which is applied to the skin of mice and causes symptoms similar to psoriasis, such as skin thickening, dryness, and scaling. We then collect skin samples to study which proteins are being cut by GzmK and how these changes may be linked to inflammation and itch.
We also use a special type of mouse called a GzmK knockout mouse. A knockout mouse has been genetically altered so that it cannot produce specific proteins like GzmK. By comparing normal mice and GzmK knockout mice after imiquimod treatment, we can see whether the absence of GzmK reduces itch and prevents changes to important skin proteins. This helps us understand exactly how GzmK contributes to psoriasis and itch.
By learning how GzmK affects both the skin and the nerves, our research may help identify new targets for treatments that reduce itch and improve the lives of people living with psoriasis.
Written by Jhunam Sidhu