In type 1 diabetes, the body attacks its own insulin-producing cells. Scientists at Helmholtz Zentrum München, partner in the German Center for Diabetes Research, and their colleagues at Technical University of Munich have now reported in the journal ‘PNAS’ about a mechanism used by the immune system to prepare for this attack. They were able to inhibit this process through targeted intervention and are now hoping this will lead to new possibilities for treatment.
Type 1 diabetes is an autoimmune disease in which the body destroys its own beta cells in the pancreas.* Researchers are still seeking to find out what causes this malfunction of the immune system in order to intervene therapeutically in the processes. A team led by Dr. Carolin Daniel, group leader at the Institute of Diabetes Research (IDF) of Helmholtz Zentrum München, has now discovered a further piece in solving this puzzle.
Treatment with an antagomir directed against miR92a results in reduced attacks of immune cells (green) on the insulin (white) producing beta cells directly in the pancreas. Moreover, the treatment leads to more regulatory T cells (red) able to protect the beta cells.
Source: Helmholtz Zentrum München
“For the first time, we were able to show that in the affected children an increased number of specific immune cells are found in the blood at the beginning of the autoimmune response,” said Daniel. She and her team had previously analyzed blood samples of children in a biobank established by Professor Anette-Gabriele Ziegler, director of the IDF, within the framework of large-scale cohort studies.
According to the authors, these special immune cells are so-called insulin-specific T follicular helper cells (TFH). They appear in the lymph nodes, among other organs, and initiate attacks of the immune system by promoting the production of antibodies by B cells. Now the scientists have found increased frequencies of these cells in samples of children with recent onset of islet cell autoimmunity – an early stage of type 1 diabetes.
In the search for the causes of the increase in TFH cells during autoimmune activation in children, the scientists discovered a previously unknown signaling pathway. “Our analyses showed that a molecule called miRNA92a** triggers a chain of molecular events, which ultimately leads to the increase in these immune cells,” said IDF doctoral student Isabelle Serr, explaining the complex mechanism. “In particular, during this process, miRNA92a interferes with the formation of important signaling proteins such as KLF2 and PTEN.”
Use in therapy and diagnostics
To check whether this newly discovered mechanism is suitable for therapeutic intervention, the scientists investigated the effect of a so-called antagomir, which specifically binds to miRNA92a molecules and blocks their effect. In an experimental model of type 1 diabetes and in the humanized model, this treatment resulted in a significantly lower autoimmune response.
“The targeted inhibition of miRNA92a or the downstream signaling pathway could open up new possibilities for the prevention of type 1 diabetes,” said Professor Ziegler. "Furthermore, the insulin-specific TFH cells could serve as biomarkers to determine the treatment success of the insulin vaccinations we perform."
* In type 1 diabetes, the insulin-producing cells in the Langerhans islets of the pancreas are destroyed because they are attacked by the body’s immune system (formation of islet autoantibodies against structures of the beta cells). As a result, the body can no longer be adequately supplied with insulin. If the destruction of the beta cells exceeds a certain degree, the disease becomes manifest and blood glucose levels rise due to insulin deficiency.
** microRNAs (miRNAs) are noncoding RNAs which play an important role in gene regulation and in particular in the inactivation of genes. In general, they have a size of 21 to 23 nucleotides, so they are very short – hence the name.
In previous studies, the researchers led by Dr. Carolin Daniel had already shown that a vaccination with optimized insulin mimetopes can slow the immune response against the beta cells of the pancreas. In particular, the regulatory T-cells of the immune system contributed to the prevention of self-destruction. https://www.helmholtz-muenchen.de/en/press-media/press-releases/2016/press-relea...
Serr, I. et al. (2016). miRNA92a targets KLF2 and PTEN signaling to promote human T follicular helper precursors in T1D islet autoimmunity, DOI: 10.1073/pnas.1606646113
The Helmholtz Zentrum München, the German Research Center for Environmental Health, pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München is headquartered in Neuherberg in the north of Munich and has about 2,300 staff members. It is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 37,000 staff members. http://www.helmholtz-muenchen.de/en
Technical University of Munich (TUM) is one of Europe’s leading research universities, with more than 500 professors, around 10,000 academic and non-academic staff, and 40,000 students. Its focus areas are the engineering sciences, natural sciences, life sciences and medicine, combined with economic and social sciences. TUM acts as an entrepreneurial university that promotes talents and creates value for society. In that it profits from having strong partners in science and industry. It is represented worldwide with a campus in Singapore as well as offices in Beijing, Brussels, Cairo, Mumbai, San Francisco, and São Paulo. Nobel Prize winners and inventors such as Rudolf Diesel, Carl von Linde, and Rudolf Mößbauer have done research at TUM. In 2006 and 2012 it won recognition as a German "Excellence University." In international rankings, TUM regularly places among the best universities in Germany. http://www.tum.de/en/homepage
The Institute of Diabetes Research (IDF) focuses on the pathogenesis and prevention of type 1 diabetes and type 2 diabetes and the long-term effects of gestational diabetes. A major project is the development of an insulin vaccination against type 1 diabetes. The IDF conducts long-term studies to examine the link between genes, environmental factors and the immune system for the pathogenesis of type 1 diabetes. Findings of the BABYDIAB study, which was established in 1989 as the world’s first prospective birth cohort study, identified risk genes and antibody profiles. These permit predictions to be made about the pathogenesis and onset of type 1 diabetes and will lead to changes in the classification and the time of diagnosis. The IDF is part of the Helmholtz Diabetes Center (HDC). http://www.helmholtz-muenchen.de/en/idf/index.html
The German Center for Diabetes Research (DZD) is a national association that brings together experts in the field of diabetes research and combines basic research, translational research, epidemiology and clinical applications. The aim is to develop novel strategies for personalized prevention and treatment of diabetes. Members are Helmholtz Zentrum München – German Research Center for Environmental Health, the German Diabetes Center in Düsseldorf, the German Institute of Human Nutrition in Potsdam-Rehbrücke, the Paul Langerhans Institute Dresden of the Helmholtz Zentrum München at the University Medical Center Carl Gustav Carus of the TU Dresden and the Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München at the Eberhard-Karls-University of Tuebingen together with associated partners at the Universities in Heidelberg, Cologne, Leipzig, Lübeck and Munich. http://www.dzd-ev.de/en/index.html
Contact for the Media
Department of Communication, Helmholtz Zentrum München – German Research Center for Environmental Health (GmbH), Ingolstädter Landstr. 1, 85764 Neuherberg, Germany – Tel. +49 (0)89 3187 2238 - Fax: +49 (0)89 3187 3324 - E-mail: email@example.com
Dr. Carolin Daniel, Helmholtz Zentrum München – German Research Center for Environmental Health (GmbH), Institute for Diabetes Research, Young Investigator Group “Immunological Tolerance in Type 1 Diabetes”, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany – Tel. +49 (0)89 3187 2188 - E-mail: firstname.lastname@example.org
Sonja Opitz | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Researchers identify how bacterium survives in oxygen-poor environments
22.11.2017 | Columbia University
Researchers discover specific tumor environment that triggers cells to metastasize
22.11.2017 | University of California - San Diego
The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.
Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.
Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
22.11.2017 | Medical Engineering
22.11.2017 | Materials Sciences
22.11.2017 | Health and Medicine