Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Autoimmune Reaction Successfully Halted in Early Stage Islet Autoimmunity

04.01.2018

Scientists at Helmholtz Zentrum München have discovered a mechanism that amplifies the autoimmune reaction in an early stage of pancreatic islet autoimmunity prior to the progression to clinical type 1 diabetes. If the researchers blocked the corresponding molecules, the immune system was significantly less active. The study was conducted under the auspices of the German Center for Diabetes Research (DZD) and was published in the journal ‘Science Translational Medicine’.

Type 1 diabetes is the most common metabolic disease in childhood and adolescence. In this disease, the body's own immune system attacks and destroys the insulin-producing cells of the pancreas. Regulatory T cells (Tregs) play an important role in this process: In healthy people, they suppress excessive immune reactions and thus prevent autoimmune diseases.


T cells after stimulation in the presence of a miRNA181a mimic. Immunofluorescent staining of the T cell marker CD4 (green), the transcription factor NFAT5 (red) and the nucleus (blue).

Source: Helmholtz Zentrum München

Dr. Carolin Daniel's team is investigating why Tregs fail to protect the islet cells in type 1 diabetes. She is a group leader at the Institute for Diabetes Research (IDF) of Helmholtz Zentrum München and a scientist in the DZD. In the current study, she and her team elucidated a mechanism that causes fewer Tregs to be produced during islet autoimmunity onset and that therefore allows the immune system to get out of control and attack.

According to the findings of the study, miRNA181a and NFAT5 molecules play a key role. "We showed that miRNA181a leads to the activation of the transcription factor NFAT5 during islet autoimmunity onset," said Daniel.* “The consequence is an inhibition of Treg induction and thus increased immune activation.“

Axis pharmacologically interrupted

In order to test the suitability of this new finding for possible therapeutic approaches, the scientists led by the first author Isabelle Serr investigated a preclinical model with early-stage islet autoimmunity. If the researchers interrupted the miRNA181a/NFAT5-axis, they observed a significantly lower activation of the immune system and an increased formation of Tregs. This was achieved both by the pharmacological inhibition of miRNA181a as well as of NFAT5.

"The targeted inhibition of miRNA181a or NFAT5 could open up new approaches to reduce the activity of the immune system against its own islet cells," said Professor Anette-Gabriele Ziegler, director of the IDF. "The combination with other immune modulating therapeutic approaches would also be conceivable as an intervention.”

In the future, the scientists want to further investigate these findings in preclinical tests. To this end, humanized models will be used to test whether the combination of insulin vaccination and inhibition of the miRNA181a/NFAT5 axis leads to a more tolerant immune system towards insulin-producing cells.

Further Information
* The researchers suspect indirect mechanisms such as the inhibition of phosphatase PTEN.

Background:
“The cooperation with Benno Weigmann's group at the University Hospital Erlangen-Nuremberg was important for the success of the research,” said Carolin Daniel. With her research group “Immunological Tolerance in Diabetes,” she is investigating the role of regulatory T cells in type 1 diabetes. She tells more in the research portrait, which includes a video interview, in which she explains how the disease develops and her strategy against it https://www.helmholtz-muenchen.de/en/research/research-excellence/portraits-of-r.... The video Type 1 Diabetes: Development and Prevention was produced by the Diabetes Information Service Munichhttps://www.diabetesinformationsdienst-muenchen.de/erkrankungsformen/typ-1-diabe... (only available in German).

Original Publication:
Serr, I. et al. (2017): A miRNA181a/NFAT5 axis links impaired T cell tolerance induction with autoimmune Type 1 diabetes. Science Translational Medicine,
DOI: 10.1126/scitranslmed.aag1782http://stm.sciencemag.org/content/10/422/eaag1782

As German Research Center for Environmental Health, Helmholtz Zentrum München pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes mellitus and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München has about 2,300 staff members and is headquartered in Neuherberg in the north of Munich. Helmholtz Zentrum München 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. https://www.helmholtz-muenchen.de/en/index.html

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). https://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.https://www.dzd-ev.de/en/index.html

Weitere Informationen:

https://www.helmholtz-muenchen.de/en/news/latest-news/press-information-news/art...

Sonja Opitz | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

More articles from Life Sciences:

nachricht World’s Largest Study on Allergic Rhinitis Reveals new Risk Genes
17.07.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Plant mothers talk to their embryos via the hormone auxin
17.07.2018 | Institute of Science and Technology Austria

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Microscopic trampoline may help create networks of quantum computers

17.07.2018 | Information Technology

In borophene, boundaries are no barrier

17.07.2018 | Materials Sciences

The role of Sodium for the Enhancement of Solar Cells

17.07.2018 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>