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 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.
Original Publication:
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]