Steatohepatitis: When killer cells run amok
Fatty liver is the most common liver disease in Germany. Around every third adult and every third overweight child have an enlarged liver due to fat deposits – and the trend is rising. Fatty liver is also the preliminary stage of fatty liver hepatitis (medical: steatohepatitis), which can lead to severe liver damage and liver cancer. A German research team has now found that if you have fatty liver inflammation, your own immune system begins to destroy the liver.
So far it has not been clear why the liver is increasingly damaged in the context of steatohepatitis, since no direct viruses, bacteria or other pathogens play a role here. Researchers at the Technical University of Munich (TUM) have now shown that auto-aggressive cells in the immune system are responsible for destroying the liver. The results were presented in the renowned journal “Nature”.
Damaging mechanism in steatohepatitis deciphered
Fatty liver hepatitis can cause severe liver damage and liver cancer. The TUM working group headed by Professor Percy Knolle has now discovered for the first time how this damage occurs and thus lays the foundation for new forms of therapy and diagnosis.
Killer cells indiscriminately destroy cells in the liver
Our own immune system, of all things, which is supposed to protect us from pathogens, is responsible for the destruction of the liver. Above all, so-called killer CD8 T cells play a decisive role here. These immune cells specifically recognize infected body cells and eliminate them. As the researchers have discovered, however, the CD8 T cells lose this ability to specifically switch off when steatohepatitis is present.
“We have discovered that the immune cells in fatty liver hepatitis are not activated by certain pathogens, but by metabolic signals,” explains lead author Michael Dudek. As a result, the immune system’s killer cells indiscriminately destroy cells in the liver.
An unfavorable combination activates killer cells
The researchers discovered a previously unknown step-by-step mechanism for activating immune cells. Using a specific sequence of inflammatory signals and products from lipid metabolism, the killer cells indiscriminately begin destroying liver tissue. “Similar to entering a security code to open a safe, the T cells are only activated by the defined sequence of activation signals armed“, Explains Head of Research Knolle.
Killer cells respond to excess ATP
According to the study, everything starts with the actually harmless metabolite adenosine triphosphate (ATP). This energy carrier is the universal form of storage for chemical energy in cells. As early as 2019, researchers at the Helmholtz Zentrum München found out that fatty liver disease is associated with a disruption of energy metabolism, which leads to increased energy storage in the liver (see article: Fatty liver: New triggers and treatment options discovered).
If ATP is outside tissue cells, the CD8 T cells react to the energy carrier and begin to destroy cells in their environment. According to the current study, this is the reason why fatty liver develops into fatty liver hepatitis.
Fatty liver hepatitis is not an autoimmune disease
The researchers point out, however, that one cannot speak of an autoimmune disease, as the mechanism discovered differs from conventional autoimmune diseases. While certain body cells are specifically attacked in autoimmune diseases, the ATP triggers an auto-aggressive state in the T cells, in which cells in the vicinity are indiscriminately destroyed.
Basis for healing treatments
Since the cause of fatty liver hepatitis is known, direct therapeutic countermeasures can now be considered for the first time. So far, the only treatment option has been to reduce risk factors such as obesity and an unhealthy diet (high in fat and sugar). “The destructive auto-aggressive form of the immune response can be clearly separated from the protective T-cell immune response against viruses and bacteria,” summarizes Knolle. He thinks it is possible to develop a therapy with which the destruction of the tissue can be prevented. (vb)
Author and source information
This text complies with the requirements of specialist medical literature, medical guidelines and current studies and has been checked by medical professionals.
Diploma-Editor (FH) Volker Blasek
- Technical University of Munich: How activated T cells destroy the liver (published: March 24th, 2021), tum.de
- P. A. Knolle,et al.: Auto-aggressive CXCR6+ CD8 T cells cause liver immune pathology in NASH; Nature, 2021, nature.com
- Susanne Seitz, Yun Kwon, Götz Hartleben, et al.: Hepatic Rab24 controls blood glucose homeostasis via improving mitochondrial plasticity, Nature Metabolism, 2019,, nature.com
- German Liver Foundation: Fatty liver inflammation (steatohepatitis) – most common liver disease in Germany (as of May 15, 2020), deutsche-leberstiftung.de
This article is for general guidance only and is not intended to be used for self-diagnosis or self-treatment. He can not substitute a visit at the doctor.
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