How a protein promotes the healing of inflammation
Inflammatory processes are a natural defense reaction of the immune system against pathogens. If they get out of control, they can however lead to diseases themselves. The protein DEL-1, is a central actor that ensures that excessive inflammation subsides. Scientists from the Medical Faculty Carl Gustav Carus of the TU Dresden and the National Center for Tumor Diseases Dresden (NCT/UCC), together with an international team of researchers, were able to demonstrate the importance and basic function of this protein. Their work could provide new approaches for the treatment of diseases such as multiple sclerosis, metabolic diseases, inflammatory bone diseases or cancer. The results of the study were now published in the journal "Nature Immunology" (www.nature.com, DOI /10.1038/s41590-018-0249-1).
Inflammation can spread like a fire and last for a long time if it is not effectively combated. The protein DEL-1 plays a central role in the body's own fire brigade. "We were able to show that DEL-1 decisively regulates the immune defense. Figuratively speaking, the protein controls a large part of the extinguishing and clean-up work. Understanding this mechanism could in future contribute to better treatments for various inflammatory diseases," said Prof. Triantafyllos Chavakis, Director of the Institute of Clinical Chemistry and Laboratory Medicine (IKL) at the TU Dresden and group leader at the DZD partner Paul Langerhans Institute Dresden.
At the beginning of an inflammatory process, certain immune cells, so-called neutrophils, migrate into the affected tissue. There they drive the inflammation as well as another cell type of the immune defense - so-called macrophages or scavenger cells - which produce inflammation-promoting substances. The protein DEL-1 forms a kind of bridge between macrophages and dying neutrophils. On the one hand, this causes the macrophages to eat dying neutrophils in a kind of clearing up action. On the other hand, DEL-1 reprograms the macrophages to produce anti-inflammatory substances. "Both are important processes that reduce inflammation and restore a healthy balance in the tissue," emphasize Dr. Ioannis Kourtzelis and Dr. Ioannis Mitroulis, scientists at IKL and NCT/UCC Dresden.
"Understanding the mode of action of DEL-1 is an important basis for developing new therapies against metabolic diseases," says Dr. Ünal Coskun of the Paul Langerhans Institute Dresden, which is operated jointly by Helmholtz Zentrum München and the University Hospital at the Technical University of Dresden. Due to its fundamental importance for the inflammatory balance, DEL-1 not only acts as a bridge between immune cells, but also connects research on various diseases. For example, inflammations also play an important role when foreign blood stem cells are transplanted to leukaemia patients. The donor's immune cells can then attack the recipient. "We are planning to investigate how the newly discovered DEL-1 mechanism can reduce the so-called graft-versus-host disease in leukaemia patients," explains Prof. Martin Bornhäuser, Managing Director at NCT/UCC Dresden and Director of Medical Clinic I at the University Hospital Dresden.
It has been known for several years that DEL-1 also plays an important role in the onset of inflammation by inhibiting the accumulation of neutrophils in tissue. The scientists have now been able to show that the different functions of the protein at different stages of the inflammatory process depend decisively on which cells secrete the body's own protein. "This location-bound principle is new. The function of molecules in tissue can depend decisively on their geographical location," said Prof. Chavakis and his long-standing cooperation partner Prof. George Hajishengallis from the University of Pennsylvania, USA.
Kourtzelis et al. DEL-1 promotes macrophage efferocytosis and clearance of inflammation. Nat Immunol. 2018 Nov 19. doi: 10.1038/s41590-018-0249-1. [Epub ahead of print]
Medical Faculty Carl Gustav Carus of the Dresden University of Technology
The University Medicine Dresden, consisting of the Medical Faculty Carl Gustav Carus and the University Hospital of the same name, has specialized in research in the fields of oncology, metabolic as well as neurological and psychiatric diseases. In these areas, the topics degeneration and regeneration, imaging and technology development, immunology and inflammation as well as prevention and care research are of particular interest. International exchange is a prerequisite for cutting-edge research - Dresden University Medicine lives this idea with staff from 73 nations and numerous collaborations with researchers and teams all over the world.
Since 2015, Dresden has been the second location of the National Centre for Tumour Diseases (NCT) after Heidelberg. The Dresden Centre is a joint institution of the German Cancer Research Centre (DKFZ), the University Hospital Carl Gustav Carus Dresden, the Medical Faculty of the Technical University of Dresden and the Helmholtz Centre Dresden-Rossendorf (HZDR).
The NCT has made it its mission to link research and health care as closely as possible. This enables cancer patients in Dresden and Heidelberg to be treated according to the latest scientific findings. At the same time, the proximity of laboratory and clinic gives the scientists important impulses for their practice-oriented research. The common goal of both locations is to develop the NCT into an international centre of excellence for patient-oriented cancer research. The Dresden Center builds on the structures of the University Cancer Center Dresden (UCC), which was founded in 2003 as one of the first Comprehensive Cancer Centers (CCC) in Germany. In 2007, the UCC was founded by the German Cancer Aid (Deutsche Krebshilfe e.V.). (DKH) as "Top Oncological Center". Since then, this award has been renewed at every reassessment.
The annual funding of the NCT/UCC Dresden will amount to 15 million euros after the start-up phase in 2019. The federal government and the Free State of Saxony will raise this amount at a ratio of 90 to 10 percent. The Free State of Saxony is providing an additional 22 million euros for the construction of a new NCT building.
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