If this defense system fails, conditions such as allergies and autoimmune diseases can develop. The German Research Foundation (Deutsche Forschungsgemeinschaft - DFG) has now approved a research application submitted by laboratories in Würzburg, Berlin and Mainz, the purpose of which is to investigate how genetic control determines the development and function of the various T cells.
"We want to find out how the individual T cells function and how their genetic regulation can be directly influenced, so that new therapy methods can ultimately be developed," explains Prof. Edgar Schmitt of the Institute of Immunology at the Johannes Gutenberg University in Mainz. The DFG has initiated the new Collaborative Research Center Transregio 52 "Transcriptional Programming of Individual T Cell Subsets" on 1 July 2008 and will be making available about € 12 million over the next four years.
T cells are white blood cells formed in the bone marrow that mature in the thymus. They can recognise invading exogenous organisms and substances and then provide a defensive response in many forms, while at the same time a specialized T cell population actively prevents any auto-aggressive immune reaction against the body's own cells.
These so-called physiological regulatory T cells have been extensively studied by Edgar Schmitt's team. "We shall be using the Transregio Collaborative Research Center to investigate how a specialized T cell develops and how it functions. In Mainz, we will be taking a closer look at the regulatory T cells, but all subpopulations of T cells will be investigated jointly with the other sites," says Schmitt. The focus is on the exact way in which the genetic information is regulated to enable these cells to systematically to carry out their functions.
If this can be established, it would be possible, for example, to switch off auto-aggressive T cells, and to influence other regulatory cells in such a way that autoimmune diseases could be prevented. "Based on our initial data, we have already been able to outline therapeutic approaches that will have a targeted effect on asthmatic diseases," explains Schmitt.
Investigations conducted by his team have shown that cyclical adenosine monophosphate (cAMP) is essential to the suppressive properties of physiological regulatory T cells. These cells have high concentrations of cAMP, and they transmit it to target cells via channels - the so-called 'gap junctions'. "As a result, these target cells are extensively inhibited and can therefore not act as central drivers of an auto-aggressive or allergic immune response such as asthma."
Schmitt and his colleagues have discovered that the so-called phosphodiesterases (PDEs) antagonize this suppression. These enzymes break down cAMP and therefore counteract inhibition by the regulatory T cells. "We were thus able to achieve a significant alleviation of asthma by systematically inhibiting these PDEs in the mouse model."
The scientists involved hope that the increase and concentration of scientific research in Germany concerning the transcriptional control of the genetic expression of T lymphocytes will contribute towards the discovery of the central trigger points of the immune reaction. The most important factors in the transcriptional control of T cells are to be identified and their function is to be decoded in in vivo mouse models, while methods of achieving targeted modulation of the transcription process are also to be researched. The institutions in Würzburg, Mainz and Berlin, with their varied expertise, will concentrate here on the cellular and molecular biological aspects of T cell biology.
Several institutions and researchers in Mainz are involved in this project: Dr Sabine Ohlemacher and HD Dr Helmut Jonuleit (dermatology), PD Dr Kerstin Steinbrink (dermatology), Prof. Susetta Finotto (1st Medical Clinic), Prof. Ari Waisman (1st Medical Clinic), HD Dr Kurt Reifenberg (Central Laboratory Animal Facility - CLAF), Dr Jürgen Siebler and Prof. Markus Neurath (1st Medical Clinic), as well as Dr Tobias Bopp and Prof. Edgar Schmitt (Institute for Immunology).
The spokesperson for the Transregio 52 Collaborative Research Center is Prof. Edgar Serfling (Pathological Institute, University of Würzburg), with Prof. Richard Kroczek (Robert Koch Institute, Berlin) and Prof. Edgar Schmitt at the University of Mainz as deputy spokespersons.
Prof. Dr. Edgar Schmitt | alfa
When Air is in Short Supply - Shedding light on plant stress reactions when oxygen runs short
23.03.2017 | Institut für Pflanzenbiochemie
WPI team grows heart tissue on spinach leaves
23.03.2017 | Worcester Polytechnic Institute
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
23.03.2017 | Life Sciences
23.03.2017 | Power and Electrical Engineering
23.03.2017 | Earth Sciences