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03 Aug 2022

New research may lead to treatments to stop the immune system mistakenly attacking the pancreas

Researchers, backed by Diabetes UK, have pinpointed differences in the genes of immune cells which could help to explain why they attack the pancreas in type 1 diabetes.

In the future, they hope the findings could help scientists to design new treatments to stop the immune attack in its tracks. 

One type of immune cell involved in the immune attack on the pancreas is called a B cell. In type 1 diabetes, B cells make proteins called autoantibodies. Autoantibodies stick to the surface of beta cells and alert killer immune cells to their presence – causing the killer cells to attack. 

But B cells have been found inside the pancreas of people with type 1 diabetes, and this has led scientists to ask if they also play a more direct role in destroying beta cells.

With funding from Diabetes UK, a team of researchers, led by Dr Jo Boldison at the University of Exeter, aimed to find new clues by studying different types of B cells and their genes.

Dr Boldison studied mice as they developed type 1 diabetes and looked at B cell samples from their pancreases.

The researchers used transcriptional analysis to make a map of all the B cell genes. This helped them to look at what happens when different combinations of B cell genes are switched on or off.

They discovered that B cells found in the pancreas as type 1 diabetes develops have different genes than B cells found elsewhere in the body. They also showed that when different subtypes of B cells arrive in the pancreas, they respond with different on-off gene combinations. 

The team identified specific genetic combinations that appeared to trigger a vicious cycle, causing B cells to respond to beta cells they’ve attacked by sending out even more damaging molecules. They also found another gene that seemed to make the immune attack worse when it was switched on. And that dialling down or switching off this gene seemed to slow down the damage.

The findings offer important insights into how different groups of B cells could contribute to the destruction of beta cells, based on patterns of gene activity. 

The next step will be to test if the same findings are seen in the human pancreas. To investigate this, the researchers plan to study pancreas samples from people with type 1 diabetes. 

With further studies, this work could help researchers to develop new immunotherapies to slow or prevent the immune attack behind type 1 diabetes.

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