Posted 15 January 2024

Exhausting study
Associate Professor Bala Krishna Murthy

As an endocrinologist and immunologist, Associate Professor Bala Krishna Murthy is keenly aware of the problems faced by people with type 1 diabetes. His research at SVI focuses on manipulating the immune system, using insights discovered in other disease areas.

“Cancer cells find ways to evade the body’s immune system so that they can continue growing. One way they do this is by ‘exhausting’ the immune cells through repetitive stimulation, removing their ability to keep the cancer at bay,” says Bala.

He explains that new immunotherapy treatments against cancer work by reenergising these exhausted immune cells, allowing them to mount a renewed offence against the offending tumour cells.

In an article published in the prestigious journal Proceedings of the National Academy of Sciences of the United States of America (PNAS), Bala turned this concept of immune exhaustion on its head, to stop immune cells from destroying insulin-producing cells in type 1 diabetes.

Bala and his team showed that, while there is some evidence of immune cell exhaustion in mice that develop type 1 diabetes, it is incomplete and not sufficient to stop the disease process.

In fact, the team showed that immune cells appear to recover from exhaustion in part by periodically moving away from the pancreas to elsewhere in the body.

“It’s almost as if they are taking a break and regaining their strength,” says Bala.

To try to exhaust the immune cells, Bala and his team selected a particular protein found in insulin producing  cells in the pancreas. The immune response to this protein is known to be involved in causing disease in diabetes-prone mice.

They genetically manipulated the mice to expose their immune cells to the protein outside of the pancreas – so that they were not able to take respite from the stimulation.

“As a result, once the cells re-entered the pancreas, they were already exhausted and no longer able to continue destroying the insulin-producing cells. These mice were then protected from developing the disease,” he says.

Although in its early days, this research holds great promise.

“Our eventual goal is to develop a short course of treatment that could be deployed in people at risk of type 1 diabetes, which would result in the condition never developing at all.”

The study, ‘Extraislet expression of islet antigen boosts T cell exhaustion to partially prevent autoimmune diabetes’, is published in PNAS.