Our immune system works around the clock to protect us from bacteria, viruses, and other harmful germs.
It also helps repair damaged tissues after injuries. One of its most important defense tools is the complement system.
This is a group of proteins that travel through the blood and work together to find and destroy dangerous invaders. For more than 100 years, scientists believed they understood how this system became activated. Now, a new study suggests there is another important pathway that had been completely overlooked.
Researchers from Mass General Brigham have discovered that a protein called granzyme K, also known as GZMK, can switch on the complement system in a surprising way.
Instead of attacking germs, this protein can trigger the complement system to attack the body’s own tissues. This causes ongoing inflammation that may damage organs and contribute to many chronic diseases. The study was published in the journal Nature.
Inflammation is a normal part of healing. When you cut your finger or catch an infection, the immune system creates inflammation to remove damaged cells and fight germs. Normally, this response fades once the danger has passed.
Chronic inflammation is different. It continues for months or even years and can slowly damage healthy tissues. Scientists believe long-lasting inflammation plays an important role in many diseases, including arthritis, psoriasis, heart disease, some brain disorders, and even the aging process.
The research was led by Carlos A. Donado, Ph.D., at Brigham and Women’s Hospital under the supervision of Michael B. Brenner, M.D. The team focused on CD8-positive T cells, a type of white blood cell that helps protect the body from infections. These cells produce GZMK.
Previous studies had found unusually high numbers of these cells in inflamed tissues from patients with rheumatoid arthritis and psoriasis. They had also been seen in cancers, cardiovascular disease, neurodegenerative diseases, and older adults. This suggested that GZMK might play a much broader role in disease than previously thought.
To investigate, the scientists studied the structure of the GZMK protein, performed laboratory experiments, examined tissue samples from people with rheumatoid arthritis, and carried out studies in animals.
They found that GZMK could activate the entire complement cascade, a chain reaction that brings more immune cells into tissues and greatly increases inflammation. As this process continues, healthy tissues become damaged.
The team then tested their findings in mice with rheumatoid arthritis and psoriasis-like skin disease. Mice that did not produce GZMK developed much milder disease. They had less inflammation, less tissue damage, and much lower complement activity. These results strongly suggest that GZMK is a major driver of chronic inflammation.
The discovery is especially exciting because many current treatments for autoimmune diseases work by suppressing large parts of the immune system. Although these medicines can reduce inflammation, they can also increase the risk of serious infections because they weaken the body’s natural defenses.
A medicine that specifically blocks GZMK might reduce harmful inflammation while allowing the immune system to continue fighting bacteria and viruses.
Co-lead author Dr. Erin Theisen said the findings suggest that targeting GZMK could help treat many different diseases where inflammation is a major problem. Senior author Dr. Michael Brenner said the research team is already working on drugs that block GZMK and hopes these treatments will provide safer and more precise options for patients.
The researchers plan to study exactly how GZMK contributes to chronic inflammation in different diseases and begin testing possible GZMK inhibitors.
If future human studies confirm these results, the discovery could lead to new treatments for rheumatoid arthritis, psoriasis, neurodegenerative diseases, cardiovascular disease, and other conditions linked to long-term inflammation.
Although more research is needed before new medicines become available, this study changes the way scientists think about the immune system. It reveals that one protein can unexpectedly turn one of the body’s strongest defense systems against its own tissues.
Understanding this process may eventually help millions of people living with chronic inflammatory diseases receive treatments that are both safer and more effective.
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.
Copyright © 2026 Knowridge Science Report. All rights reserved.
