Our immune system works like a personal bodyguard, protecting us every day from infections and injuries.
One of the key tools it uses is something called the complement system, a group of proteins that help find and destroy harmful germs.
But now, scientists have discovered that this powerful defense system can sometimes turn against us and hurt our own body.
Researchers from Mass General Brigham found a protein called granzyme K (GZMK) that can mistakenly trigger the complement system to attack healthy tissues. This causes long-lasting inflammation and damage.
Their discovery, published in the journal Nature, changes what we’ve believed for over 100 years about how this system works. Most importantly, this could lead to new ways to treat autoimmune diseases without weakening our ability to fight infections.
The study was led by Dr. Carlos Donado at Brigham and Women’s Hospital and guided by Dr. Michael Brenner. The team looked at a type of immune cell called CD8+ T cells, which make the protein GZMK. These cells are found in inflamed body parts of people with diseases like rheumatoid arthritis and psoriasis.
They also show up in the brains of people with Alzheimer’s disease, in damaged hearts, in cancerous tissues, and even in older people. Since these cells were seen in so many illnesses, scientists wondered if GZMK was a main reason for chronic inflammation.
To find out, the researchers first studied what GZMK looks like and how it compares to other proteins. They then tested to see if GZMK could activate the complement system. They also studied tissue samples from people with rheumatoid arthritis and used animal models to understand how GZMK works in living organisms.
The results were clear. GZMK activates the entire complement system. This leads to more inflammation, brings in other immune cells, and causes tissue damage. In mice that were specially bred to lack GZMK, the scientists saw that they had less inflammation, milder arthritis and skin problems, and lower complement activity.
This means that blocking GZMK could be a powerful way to stop inflammation without harming the rest of the immune system.
Today’s treatments for autoimmune diseases often shut down large parts of the immune system, which can lead to more infections. But if doctors can block GZMK specifically, they might be able to stop the damaging inflammation while keeping the body safe from infections.
Dr. Erin Theisen, who co-led the study, said this discovery could help treat many diseases where inflammation is a problem. Dr. Brenner added that they are now working on medicines that can block GZMK, hoping to make safer treatments with fewer side effects.
Next, the researchers will study how GZMK causes inflammation in different illnesses. They also plan to test new drugs that block GZMK in people. This could lead to better treatments for arthritis, psoriasis, brain diseases, heart problems, and even age-related inflammation.
This discovery changes how we understand the immune system. If scientists can develop safe ways to stop GZMK, millions of people with chronic inflammation could have better, safer treatments. It’s a huge step forward in the fight against many long-term health problems.
If you care about heart health, please read studies that Changing blood pressure readings is a hidden sign of heart disease and common type 2 diabetes drugs may raise heart risk.
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