Targeting "boot camp" enzyme could fight autoimmune diseases and cancer
A new understanding of the way the body teaches immune cells to fight off threats has raised hopes of advanced treatments for autoimmune conditions, and possibly other diseases such as cancer. The discovery centers on an enzyme that plays a key role in what researchers describe as a "boot camp" for immune cells, which they say can be targeted to both dial up or turn down an immune response depending on the task at hand.
The study was led by researchers at the Walter Eliza Hall Institute (WEHI) in Australia, who were investigating the way an organ called the thymus shapes human immunity. This gland sits next to the heart and is referred to as a"boot camp" because it produces important immune cells called T cells up until we reach puberty. Here, it teaches them to fight infection and leave healthy organs unharmed by showing them a preview of the healthy tissues they will encounter as they move around the body.
This preview is overseen by a protein called the Autoimmune Regulator (AIRE), which activates the thousands of genes needed for the healthy tissue training. What has remained unclear, and what the WEHI scientists set out to investigate, was how AIRE knew which genes it needed to switch on.
The team's experiments involved mice engineered to be lacking an enzyme called KAT7, which turned out to have profound consequences for their immune systems. By using a novel drug to block its function in these pre-clinical models, the scientists found that they could essentially supercharge the immune system, which resulted in the development of various autoimmune conditions.
“We showed how a KAT7 inhibitor, developed in collaboration with Jonathan Baell at Monash University, was able to stop AIRE from switching on the genes needed to properly train immune T cells," said study author Professor Tim Thomas. "Stopping this process sent the immune system into overdrive, leading to immune T cells going rogue and causing a range of autoimmune conditions in pre-clinical models. This shows a clear link between KAT7 and AIRE in maintaining immune tolerance."
The other side of this coin presents potential new treatments for conditions where an elevated immune response is desirable. This could have ramifications in the field of immunotherapy, where scientists are searching for ways to boost the body's natural defenses against cancer. The study shows that focusing on KAT7 to alter the training program for T cells is one way this could be achieved.
“Our research shows KAT7 could be targeted to modify the training of immune T cells so they can either be stopped from causing autoimmunity, or boosted to fight disease," said study author Daniel Gray. “Potential applications of this knowledge include organ-specific autoimmune diseases such as type 1 diabetes and multiple sclerosis, as well as cancer immunotherapy. In the latter scenario, the immune system could be supercharged to combat cancer by blocking KAT7 in the thymus."
The research was published in the journal Science Immunology.
Source: Walter Eliza Hall Institute