Our researchers have pinpointed differences in the genes of immune cells which could help explain why they attack the pancreas in type 1 diabetes. In the future, the findings could help scientists design new treatments to stop the immune attack in its tracks.
Our immune system has the job of destroying bacteria and viruses that invade our body. But in type 1 diabetes, the immune system mistakenly attacks and destroys insulin-producing beta cells in the pancreas.
We don’t fully understand why this happens, but our researchers are on the case. In a new study, they’ve investigated the immune system in minute detail to better understand the origins of type 1 diabetes.
The immune system’s A B Cs
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 our funding, a team of researchers led by Dr Jo Boldison at University of Exeter aimed to find new clues by studying different types of B cells and their genes.
All our cells have thousands of genes. Genes are like instruction manuals that tell our cells what to do. Genes can be ‘switched’ on or off, or even ‘dialled’ up or down, and this affects the way that cells behave.
Dr Boldison studied mice as they developed type 1 diabetes and looked at B cell samples from their pancreases. The researchers used a technique, called 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 switched off.
Looking for an immune off switch
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.
Going back to square 1 for type 1
Our researchers’ new findings give us important insights into how different groups of B cells could contribute to the destruction of beta cells, based on patterns of gene activity.
We need to keep in mind that this is very early-stage research, looking at mice. 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 treatments, called immunotherapies, designed to slow or prevent the immune attack behind type 1 diabetes. New therapies that specifically target the damaging B cells and gene combinations, and leave other parts of the immune system untouched, could be especially effective.
You can read more about our immunotherapy research.
