Our immune system is constantly working to protect us from infections and injuries.
One of its most powerful tools is the complement system, a network of proteins that detects and eliminates harmful invaders.
However, researchers at Mass General Brigham have made a groundbreaking discovery: a protein called granzyme K (GZMK) can activate the complement system against the body’s own tissues, leading to chronic inflammation and tissue damage.
This discovery, published in Nature, challenges over 100 years of understanding about how the complement system works.
It also opens the door for new treatments that could block this harmful process without interfering with the body’s ability to fight infections.
How GZMK Drives Inflammation
The study was led by Carlos A. Donado, Ph.D., at Brigham and Women’s Hospital, under the supervision of Michael B. Brenner, M.D. The research focused on CD8+ T cells, a type of immune cell that produces GZMK.
These cells are highly active in inflamed tissues of patients with rheumatoid arthritis, psoriasis, and other inflammatory diseases.
Other studies have also found these cells in the diseased tissues of patients with neurodegenerative diseases, cardiovascular diseases, cancer, and even aging individuals. Their presence in so many conditions led researchers to suspect that GZMK plays a fundamental role in inflammation.
To investigate, the researchers:
Analyzed the protein structure of GZMK to compare it with other known proteins.
Conducted experiments to see if GZMK activates the complement system.
Studied rheumatoid arthritis tissues and animal models to confirm GZMK’s effects.
Their findings showed that GZMK can activate the entire complement cascade, leading to:
- Increased inflammation
- Recruitment of immune cells
- Tissue damage in affected organs
Proof in Animal Models
The researchers also tested the role of GZMK in two animal models:
1️⃣ Rheumatoid arthritis model
2️⃣ Psoriasis-like skin inflammation model
Mice that lacked GZMK were significantly protected from disease, showing:
Less inflammation
Reduced arthritis and skin disease
Lower complement activation
This confirmed that GZMK is a key driver of inflammation and could be a powerful target for new treatments.
Potential for Targeted Therapies
Current treatments for autoimmune diseases often suppress the entire immune system, increasing the risk of infections. The exciting promise of GZMK-targeted therapies is that they could:
Block harmful inflammation
Preserve the body’s natural defenses against infections
Dr. Erin Theisen, co-lead author of the study, emphasized the importance of these findings:
“These results highlight the broad potential of targeting GZMK in multiple diseases where inflammation plays a role.”
Dr. Michael Brenner, senior author, added that the team is now working on developing GZMK inhibitors. Their goal is to create precise treatments for autoimmune and inflammatory diseases that could improve patient outcomes without major side effects.
What’s Next?
The researchers plan to:
Further study how GZMK contributes to chronic inflammation in different diseases.
Develop and test GZMK-blocking drugs to see if they can be effective in humans.
Explore how these findings can be applied to conditions like arthritis, psoriasis, neurodegenerative diseases, and even aging-related inflammation.
Final Thoughts
This discovery represents a major shift in our understanding of the immune system. By identifying GZMK as a key driver of inflammation, scientists have uncovered a potential new approach to treating autoimmune diseases.
If successful, targeting GZMK could lead to safer and more effective treatments for millions of people suffering from chronic inflammatory conditions—a breakthrough that could change the future of medicine.
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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