Researchers say c-Rel protein could delay onset of type 1 diabetes

US researchers have identified a potential root cause for the dysfunctional immune response seen in type 1 diabetes, and report that a protein called c-Rel could delay onset of the disease.
In type 1 diabetes, immune cells (known as T cells) are impaired and struggle to maintain a balance between preserving healthy cells and destroying injured cells.
This problem leads to certain T cells destroying insulin-producing pancreatic beta cells, and researchers have long been studying the reasoning behind this.
Scientists at Case Western Reserve University School of Medicine investigated the c-Rel protein due to its use in previous studies that found it can protect against autoimmunity in diseases such as arthritis.
Lead author Parameswaran Ramakrishnan explained that the c-Rel protein is required for the function of two different T cells called T-lymphocytes. The two cells have opposing functions: one can become overactive and attack healthy tissue, and the other helps suppress this activity.
The study team developed genetically engineered mice that lacked c-Rel, and then measured their T cell numbers.
They found that the mice without c-Rel had a reduction in cells that are needed to suppress autoimmunity, known as T regulatory cells (Tregs).
The lack of these Treg cells led to enhanced proliferation of T cells that carry out immune response, suggesting that they were overworking to compensate for the absent Tregs.
All of the mice without c-Rel developed type 1 diabetes by 17 weeks of age; whereas 80 per cent of the control mice developed diabetes by 25 weeks of age.
Significantly, the researchers reversed this accelerated development when the mice lacking c-Rel were supplemented with Tregs. All the mice still went on to develop diabetes.
“We were expecting that absence of c-Rel will prevent spontaneous diabetes development in non-obese diabetic mice,” said Ramakrishnan. “But to our surprise, we found an opposite effect, where 100% of the c-Rel deficient animals developed the disease at a twice faster rate.”
The researchers will now use this model to enhance c-Rel research into immune regulation in type 1 diabetes, and plan to evaluate unique forms of c-Rel in future studies.
The findings appear online in Diabetes, a journal of the American Diabetes Association.