Auto-aggressive immune cells cause liver immune pathology in non-alcoholic steatohepatitis Skip to content Menu Medical Home Life Sciences Home Become a Member Search Medical Home Life Sciences Home About Functional Food News Health A-Z Drugs Medical Devices Interviews White Papers More... 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Mar 24 2021 Non-alcoholic steatohepatitis (NASH), often called 'fatty liver hepatitis', can lead to serious liver damage and liver cancer. A team of researchers at the Technical University of Munich (TUM) has discovered that this condition is caused by cells that attack healthy tissue - a phenomenon known as auto-aggression. Their results may help in the development of new therapies to avoid the consequences of NASH. Fatty liver disease (NASH) is often associated with obesity. However, our understanding of the causes has been very limited. A team working with the immunologist Prof. Percy Knolle of TUM has now explored this process step by step in model systems based on mice - and gained promising insights into the mechanisms causing NASH in humans. "We have seen all of the steps observed in the model systems in human patients," says Prof. Knolle. The team's results will be published in Nature . Auto-aggressive immune cells destroy liver tissue The immune system protects us against bacteria and viruses and the development of cancerous tumors. The so-called CD8 killer T cells play an important role here. They specifically recognize infected body cells and eliminate them. With fatty liver hepatitis, the CD8 T cells have lost this targeted deactivation ability. We have discovered that, in NASH, the immune cells are not activated by certain pathogens, but rather by metabolic stimuli. The T cells activated in this way then kill liver cells of all types." Michael Dudek, Study's First Author Sequential activation of T cells Until that point, the immune cells undergo a unique, step-by-step - and previously unknown - activation process. The T cells develop their auto-aggressive properties only when exposed to inflammation signals and products of fat metabolism in the right order. "Like when we use the combination to unlock a safe, the T cells are switched to 'deadly mode' only through the defined sequence of activation stimuli," says Prof. Knolle, a professor of molecular immunology at TUM. As the trigger for the killing of tissue cells, the international team of researchers identified a basically harmless metabolite: the presence of the energy-carrying molecule ATP outside cells. When auto-aggressive CD8 T cells in the liver reacted with ATP, they destroyed nearby cells, thus causing NASH. Auto-aggression, but not an auto-immune disorder The destruction of tissue through auto-aggressive immune cells, as discovered by the researchers, differs from familiar auto-immune disorders, in which immune system cells specifically attack certain cells in the body. The authors note, however, that the tissue-destroying auto-aggressive T cells may also play a role in auto-immune pathologies that has yet to be discovered. New therapies for fatty liver hepatitis Until now, the only way of reversing the effects of fatty liver hepatitis was to eliminate the underlying factors - namely obesity and a high-calorie diet. In other words, patients had to change their lifestyles. The realization that the disease is caused by activated immune cells now suggests possibilities for the development of new therapies. "The destructive auto-aggressive form of the immune response is fundamentally different from the protective T cell immune response to viruses and bacteria," says Prof. Knolle. He is confident that further research can identify targeted immunotherapies that simply prevent the destruction of tissue. Source: Technical University of Munich (TUM) Journal reference: Dudek, M., et al. (2021) Auto-aggressive CXCR6+ CD8 T cells cause liver immune pathology in NASH. Nature. doi.org/10.1038/s41586-021-03233-8 . Posted in: Cell Biology Comments (0) Download PDF Copy Suggested Reading Study explores whether a bidirectional causal link exists between MASLD and sarcopenia Do cocoa flavanols influence heart and fatty liver risk factors? SynGenSys introduces Liver.SET synthetic promoter library for liver-specific gene expression for in vivo gene therapies Researchers develop new score to predict the risk of liver cancer Cornell study finds existing drug could boost liver cancer immunotherapy A dual-action approach to preventing hepatocellular carcinoma Diagnostic prognostic and therapeutic relevance of PIVKA-II in hepatocellular carcinoma Bacterial infections in patients with liver cirrhosis show rising prevalence and high mortality Comments The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical. 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The Role of Spectroscopy in Real-Time Analysis Latest Life Science News From liquid handling to sample storage Study explores how reversible RNA editing could transform future cardiovascular medicine Hamilton Storage completes full transition to green refrigerants across automated portfolio Alzheimer’s plaques decline

…It Matters For Vascular Health What Is the Difference Between siRNA and shRNA Knockdown Methods? What Is Bio-Monitoring? The Role of Spectroscopy in Real-Time Analysis Latest Life Science News From liquid handling to sample storage Study explores how reversible RNA editing could transform future cardiovascular medicine Hamilton Storage completes full transition to green refrigerants across automated portfolio Alzheimer’s plaques decline after CAR-T immune cell treatment in preclinical study Eppendorf collaborates with Dubai Police to automate forensics l…

When auto-aggressive CD8 T cells in the liver reacted with ATP, they destroyed nearby cells, thus causing NASH.

… researchers identified a basically harmless metabolite: the presence of the energy-carrying molecule ATP outside cells. When auto-aggressive CD8 T cells in the liver reacted with ATP, they destroyed nearby cells, thus causing NASH . Auto-aggression, but not an auto-immune disorder The destruction of tissue through auto-aggressive immune cells, as di…

The T cells develop their auto-aggressive properties only when exposed to inflammation signals and products of fat metabolism in the right order.

…T cells Until that point, the immune cells undergo a unique, step-by-step - and previously unknown - activation process. The T cells develop their auto-aggressive properties only when exposed to inflammation signals and products of fat metabolism in the right order . "Like when we use the combination to unlock a safe, the T cells are switched to 'deadly mode' only through the defined…