Discovery of an immune system molecule could help to boost the immunity of people with a predisposition to type 1 diabetes. JDRF researchers found that high levels of this molecule known as PEPITEM could restore normal immune T cell function and therefore reverse or stop the T1D autoimmune attack.


These researchers identified that PEPITEM controls the movement of immune cells from the blood into tissue during an inflammatory response in the immune system. In autoimmune diseases such as type 1 diabetes and rheumatoid arthritis, this pathway is disrupted resulting in inappropriate inflammation. Interestingly, control of this pathway also declines in the normal ageing process.

The study, published in Nature Medicine, shows how in a healthy immune system, PEPITEM tightly controls the level of response to infection and disease. PEPITEM is secreted by the beta cells of the immune system, and stops inflammatory T cells moving from blood into tissue. In people with type 1 diabetes the level of PEPITEM is reduced, meaning the damaging T cells can access vulnerable tissue.

After investigation in both cells and mouse models, study researchers tested their PEPITEM theory in humans. In the study, blood samples were taken from people with T1D or rheumatoid arthritis and compared with blood from healthy people. The samples showed that PEPITEM levels, as well as other key components of the pathway, were reduced in people with T1D and rheumatoid arthritis. Importantly, the researchers found that raising PEPITEM levels had the potential to restore normal T cell function in these individuals, giving promise for the development of future therapies to help restore normal immune system functionality.

Lead investigator Professor Ed Rainger explained: “Our discovery of this new pathway is very exciting. Not only does it reveal new ways in which our bodies control inflammation, it also indicates that we may be able design new drugs to reverse the disease and age specific loss of this pathway”.

The next step is to use the findings of this study in clinical studies investigating new therapies and treatments that target this pathway, potentially restoring normal regulation of the immune system and preventing the autoimmune response that leads to type 1 diabetes.

To access the journal article, click here.



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