Type 1 diabetes affects 30,000 individuals throughout Germany and is the most common metabolic disease in children and adolescents. To halt the ever-increasing incidence, the young investigator group "Immunological Tolerance in Type 1 Diabetes" at the Institute of Diabetes Research directed by Prof. Dr. Anette-Gabriele Ziegler is exploring new strategies to prevent the onset of the disease.
In the current study, the scientists investigated the effect of specifically modified insulin mimetopes on the immune system.* "In particular, we wanted to find out whether we can induce the protective regulatory T cells to produce a tolerance of the body against insulin, if we bring them into contact with our novel peptides," said Dr. Carolin Daniel, who leads a young investigator group and directs the study.
Optimized mimetopes curb the immune system
The study is based on findings Daniel made several years ago at Dana Farber Cancer Institute and Harvard Medical School in Boston. There she showed that insulin mimetopes she optimized were significantly more efficient in inducing a tolerance through regulatory T cells towards insulin than their natural counterparts (epitopes). In young mice, the induction of insulin mimetopes at low doses completely halted the development of type 1 diabetes.
The next step was achieved in the study that has just been published: In a so-called humanized mouse model, whose immune system is very similar to that of humans, the scientists were able to confirm the results** -- an important indication for the effectiveness of the optimized human insulin mimetopes.
"In fact, we were able to show that the new vaccine efficiently stimulates the regulatory T cells, which then can impede the attack of the immune system on the insulin-producing cells," said lead author Isabelle Serr, who was involved in the study within the framework of her dissertation.
In the long term Daniel and her group want to further develop the method for preventive treatment of children at high risk for type 1 diabetes. "An important step will be to test the new therapy clinically -- that is our vision," said Daniel with regard to the future.
* In patients with type 1 diabetes, the insulin-producing cells in the islets of Langerhans of the pancreas are destroyed because they are attacked by the body's own immune system (formation of islet autoantibodies against structures of beta cells). As a result, the pancreas can no longer supply the body with sufficient insulin. If the destruction of the beta cells exceeds a certain extent, the disease breaks out and blood glucose levels rise due to the lack of insulin.
** The investigation of complex biological processes requires in vivo studies. Here the mouse is a preferred experimental model. Unfortunately, the transferability of such experiments to the human organism is not always given. Therefore, models in which human cells or tissue can be studied in an animal are becoming increasingly important. The "humanized mouse" represents an especially attractive translation model for studying diseases of the immune system. The benefits of such a model, however, depend on the ability to accurately mimic the human immune system. For this purpose, mouse models are used such as the HLA-DQ8 NOD/scid-IL2rgnull mouse model, which lacks an own murine immune system. These mouse models, for example, are reconstituted with human hematopoietic stem cells and subsequently enable successful engraftment and the development of a human immune system to study relevant processes in vivo.
Materials provided by Helmholtz Zentrum München - German Research Center for Environmental Health. Note: Content may be edited for style and length.
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