Dr. Carolin Daniel

Peacekeeping Troops of the Immune System against Type 1 Diabetes

Carolin Daniel compares research to studying a mosaic: “If you look at it from a distance, you see a coherent picture. However, viewed up close, in each single mosaic piece you will find another hidden mosaic that first must be elucidated in detail.“ For Carolin Daniel and her junior research group “Immunological Tolerance in Type 1 Diabetes” at the Institute of Diabetes Research, the overall mosaic is type 1 diabetes, and the special mosaic piece is the role of regulatory T cells, the so-called peacekeeping troops of the body’s own immune system. 

Carolin Daniel explores strategies for the prevention of autoimmune diseases such as type 1 diabetes. A vaccine she developed, which mimics natural insulin, stimulates the formation of regulatory T cells (stained blue in the image), which protect the insulin-producing islet cells (green) against the attack of the immune system. Source: HMGU

More and more children are being diagnosed with type 1 diabetes. In this autoimmune disease the body’s own immune cells gradually destroy the insulin-producing beta cells of the pancreas. The disease could be markedly reduced if Carolin Daniel succeeds in applying to humans what she has already achieved on a model organism as a postdoc in Boston: By means of an insulin variant she has induced regulatory T cells to protect the beta cells against an attack of the body’s own immune system, thereby leading to the prevention of type 1 diabetes.

Daniel’s objective is to translate this breakthrough in immunology from the animal model to benefit human patients. Together with her team of five, she is seeking to develop a vaccine that can prevent the onset of type 1 diabetes in childhood.

The disease has a strong genetic component, which is likely triggered by environmental factors. The main trigger, however, is ultimately a false reaction of the immune system in which the produced immune cells do not distinguish between foreign and endogenous components. Normally in such a case, regulatory T cells move to the scene and prevent an attack on the body’s own cells. Daniel therefore refers to the regulatory T cells as the “blue helmets, the peacekeeping troops of the immune system”. However, in type 1 diabetes, sufficient numbers of these “blue helmets” are lacking to carry out this function. The beta cells in the pancreas that produce insulin can be destroyed over a period of time by the pathologically activated immune cells.

Daniel‘s therapy concept is to strengthen the peacekeeping troops: It is based on converting naive T cells into regulatory T cells with respect to the specific antigen. In this case, insulin functions as the antigen. That is why researchers first attempted to generate regulatory T cells via stimulation with low doses of insulin. This method proved to be inefficient, and the researchers subsequently used higher doses of insulin. Daniel laughs: “That went according to the motto “more helps more”. In fact, through this method diabetes was partially triggered in the model – but regulatory T cells could not be efficiently produced.”

Instead of quantity, Daniel focused on quality. She developed an insulin variant, which has now been patented, in which a low dose actually leads to the desired result. With her team, the immunologist is now working from an insulin mimetic compound modeled after the natural epitope to develop an equivalent vaccine for humans.

Daniel is convinced that Helmholtz Zentrum München offers her the best conditions to achieve her goal. Here she has access to extensive data and biological samples from children and adults. The material was collected by the director of the Institute of Diabetes Research, Anette-Gabriele Ziegler, in part over a period of 20 years. “The data and samples are a gold mine for research and are essential to develop strategies for the prevention of type 1 diabetes and autoimmunity,” Carolin Daniel points out.