Our immune system works day and night to protect us from bacteria, viruses, and injuries. It is a complex defense network made up of many types of cells and proteins that cooperate to keep the body healthy.
When this system works properly, it identifies harmful invaders and removes them before they cause serious damage. However, when the immune system becomes confused or overactive, it can begin attacking the body’s own tissues. This mistaken attack can lead to long‑lasting inflammation and diseases such as rheumatoid arthritis and psoriasis.
One important part of the immune system is known as the complement system. Scientists first discovered this system more than one hundred years ago. It is made up of a group of proteins that circulate in the blood and body fluids. When these proteins detect danger, they activate one another in a chain reaction.
This process helps mark harmful microbes, attract immune cells to the site of infection, and destroy invaders. For decades, scientists believed that the complement system was mainly triggered by microbes or by antibodies that attach to foreign targets.
Now researchers from Mass General Brigham have discovered something surprising. A protein produced by immune cells can activate this powerful defense system against the body’s own tissues.
This protein is called granzyme K, often shortened to GZMK. The discovery suggests that some forms of chronic inflammation may begin in a completely different way than scientists previously thought.
The research was led by Carlos A. Donado, Ph.D., at Brigham and Women’s Hospital, working under the supervision of Michael B. Brenner, M.D. Their findings were published in the scientific journal Nature.
The study focused on a group of immune cells called CD8 positive T cells. These cells normally help the body destroy infected or damaged cells. They produce several substances that can kill dangerous targets. One of these substances is granzyme K.
In recent years, scientists noticed that CD8 T cells that produce granzyme K appear in large numbers inside inflamed tissues. Doctors have found these cells in patients with rheumatoid arthritis and psoriasis, two common inflammatory diseases.
Researchers have also reported seeing similar cells in tissues affected by neurodegenerative diseases, heart disease, cancer, and even in the bodies of older adults. Because these cells appear in so many different conditions, scientists began to suspect that granzyme K might play an important role in driving inflammation.
To investigate this possibility, the research team carefully examined the structure of the granzyme K protein and compared it with other known proteins involved in immune reactions.
They also carried out laboratory experiments to see whether granzyme K could activate the complement system. In addition, they analyzed tissue samples from patients with rheumatoid arthritis and conducted experiments using animal models of inflammatory disease.
The results were striking. The scientists found that granzyme K could start the entire complement cascade, the chain reaction that activates many complement proteins. Once this cascade began, it caused strong inflammatory signals.
Immune cells were drawn to the affected tissues, and damage to surrounding tissue increased. This suggested that granzyme K could act as a powerful trigger that drives inflammation even when no infection is present.
The researchers then tested their idea using mice. They studied two disease models: one that mimics rheumatoid arthritis and another that produces psoriasis‑like skin inflammation. In these experiments, some mice were genetically engineered so they could not produce granzyme K. These animals showed far less disease than normal mice.
They had lower levels of inflammation, milder arthritis symptoms, and reduced skin damage. The complement system was also much less active in these mice. These findings strongly suggested that granzyme K is an important driver of inflammatory disease.
This discovery could have important medical benefits. Many current treatments for autoimmune diseases work by suppressing the entire immune system. While these drugs can reduce inflammation, they also weaken the body’s ability to fight infections. This can leave patients more vulnerable to illness.
The new findings suggest another possibility. If scientists can develop medicines that block granzyme K, they might be able to stop harmful inflammation without shutting down the entire immune system. This could allow the body to continue fighting infections while preventing damage to healthy tissues.
Dr. Erin Theisen, a co‑lead author of the study, explained that targeting granzyme K could help treat a wide range of diseases linked to inflammation. Because this protein appears in many different conditions, therapies that block it might benefit patients with arthritis, psoriasis, and possibly other chronic diseases.
Senior author Dr. Michael Brenner said the research team is already working on ways to develop drugs that can block granzyme K safely. Their goal is to design treatments that focus precisely on the harmful pathway discovered in this study.
In the future, researchers plan to explore how granzyme K contributes to inflammation in many different diseases. They also hope to test potential granzyme K inhibitors to see whether they can work safely in humans. If successful, these treatments could represent a new strategy for controlling chronic inflammation and improving the lives of millions of patients around the world.
If you care about inflammation, please read studies about turmeric: nature’s golden answer to inflammation, and what to eat to reduce chronic Inflammation.
For more health information, please see recent studies about how a plant-based diet could help ease inflammation ,and Vitamin D deficiency linked to increased inflammation.
The research findings can be found in Nature.
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