Researchers at Northwestern Medicine have uncovered a new mechanism that controls a special group of immune cells known as regulatory T-cells (Tregs).
These cells play a crucial role in managing the body’s immune response, and the discovery could lead to new treatments for inflammatory disorders and cancer.
The findings were published in the journal Immunity.
Tregs are a small but important group of T-cells that help prevent the immune system from overreacting.
They help control inflammation and prevent autoimmune diseases, where the body attacks its own tissues. However, if Tregs lose their ability to function properly, they can cause severe inflammation and other health problems.
The study, led by Dr. Booki Min, a professor of Microbiology-Immunology at Northwestern University, focused on a protein called Lymphocyte activation gene 3 (Lag3).
This protein is found on Tregs and other types of T-cells.
Although Lag3 was known to be important for Treg function, the exact role it plays was not well understood.
To explore this, Dr. Min’s team used specially designed mouse models in which only the Tregs lacked Lag3. They also used advanced techniques like RNA sequencing and flow cytometry to study how Lag3 affects Treg function.
The researchers discovered that Lag3 is essential for Tregs to control autoimmune inflammation in the central nervous system.
When Lag3 was missing, the Tregs showed high levels of a gene called Myc, which is involved in controlling how cells produce energy.
This led to a shift in the Tregs’ energy production, making them rely on glycolysis (a less efficient way of producing energy) instead of oxidative phosphorylation, which is a more efficient process.
Without Lag3, the Tregs became less effective at controlling inflammation because their energy production was disrupted. However, when the researchers reversed this process, the Tregs regained their ability to suppress inflammation.
According to Dr. Min, these findings are significant because they show how Lag3 controls Treg function by limiting Myc expression and managing the cells’ energy use. This discovery could lead to new therapies for autoimmune diseases by boosting Treg function. It could also be useful in cancer treatment, where reducing Treg function might help the immune system fight tumors more effectively.
“This research offers new possibilities for targeting Lag3 in different diseases. In autoimmune conditions, we may need to strengthen Treg function, while in cancer, we might need to weaken it to help the immune system fight tumors,” Dr. Min explained.
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