Too much of a protein called c-FLIPR can trigger autoimmune diseases
As strange as it may seem, a process called "cellular suicide" is actually crucial for the survival of the entire body. A protein called c-FLIPR plays a key role in controlling this process, which is called "apoptosis".
Scientists at the Helmholtz Centre for Infection Research (HZI) have described the significance of c-FLIPR for the immune system in more detail: In the presence of an excess of this molecule, mice can fight infectious diseases better, but they develop autoimmune diseases as they get older. The inhibitory effect of c-FLIPR on apoptosis is the underlying cause of both these effects.
Apoptosis is used by cells that are changed by disease or are simply not needed any longer to eliminate themselves before they become a hazard to the body—on a cellular level, death is part of life. Disruption of this process can lead to cancer or immunodeficiencies, but also to autoimmune diseases, in which cells attack their own body.
HZI scientist Prof Ingo Schmitz and his team investigate the regulation of apoptosis in the immune system. In collaboration with researchers of the Otto von Guericke University Magdeburg and the Helmholtz Zentrum München, they elucidated the role of a central protein in this process.
The researchers published their results in "Cell Death & Disease". So-called c-FLIP proteins inhibit signaling cascades that can lead to apoptosis. This is important temporarily in the response to pathogens to ensure that lymphocytes, a type of immune cells, can proliferate sufficiently. Towards the end of the immune response, once the lymphocytes completed their tasks and successfully eliminated the pathogen, c-FLIP is usually degraded. As a result, apoptosis is enabled again, the lymphocytes die and the equilibrium in the immune system is restored.
The HZI researchers then took a closer look at the exact function of a certain variant of the protein, called c-FLIPR. They used mice to investigate what happens if this protein is always present in lymphocytes and other blood cells. Whereas the apoptosis inhibitor caused no anomalies in young mice, the scenario in older mice was quite different: "The composition of the lymphocytes was changed significantly," says Schmitz. "Furthermore the immune cells were strongly activated."
The overactivation is easily apparent in the body. The researchers found immune molecules, called autoantibodies, which attack the body's own tissue in the kidneys and lung. In addition, they detected harmful protein deposits in the kidneys. The changes in the lung tissue are also indicative of the immune system attacking its own body in the presence of too much c-FLIPR. "Immune cells migrate into the lung and attack the lung tissue," says Schmitz. Physicians usually see these symptoms in a human autoimmune disease called systemic lupus erythematosus
The HZI scientists discovered already last year that cells can fight bacterial infections better if c-FLIPR is turned on permanently. This means that inhibiting the suicide of cells has beneficial effects in acute infections, but leads to autoimmune reactions in the long run. "c-FLIPR is important for the balance of the immune system. It might be possible to intervene with suitable therapeutic agents if the equilibrium of the immune system is disrupted," says Schmitz.
Frida Ewald, Michaela Annemann, Marina C. Pils, Carlos Plaza-Sirvent, Frauke Neff, Christian Erck, Dirk Reinhold, Ingo Schmitz
Constitutive expression of murine c-FLIPR causes autoimmunity in aged mice
Cell Death & Disease, 2014
The research group "Systems-oriented Immunology and Inflammation Research" studies the molecular processes that sensitize immune cells to the body’s own tissues. A main focus is on the cellular suicide programme apoptosis.
The Helmholtz Centre for Infection Research (HZI)
Scientists at the Helmholtz Centre for Infection Research in Braunschweig, Germany, are engaged in the study of different mechanisms of infection and of the body’s response to infection. Helping to improve the scientific community’s understanding of a given bacterium’s or virus’ pathogenicity is key to developing effective new treatments and vaccines.
Dr. Birgit Manno | Helmholtz-Zentrum
Why do animals fight members of other species?
24.04.2015 | University of California - Los Angeles
Is a small artificially composed virus fragment the key to a Chikungunya vaccine?
24.04.2015 | Paul-Ehrlich-Institut - Bundesinstitut für Impfstoffe und biomedizinische Arzneimittel
KAIST researchers published an article on the development of a novel technique to precisely track the 3-D positions of optically-trapped particles having complicated geometry in high speed in the April 2015 issue of Optica.
Daejeon, Republic of Korea, April 23, 2015--Optical tweezers have been used as an invaluable tool for exerting micro-scale force on microscopic particles and...
A very small and rare species of shark is swimming its way through scientific literature. But don't worry, the chances of this inches-long vertebrate biting...
Ever since computers have been small enough to be fixtures on desks and laps, their central processing has functioned something like an atomic Etch A Sketch, with electromagnetic fields pushing data bits into place to encode data.
Unfortunately, the same drawbacks and perils of the mechanical sketch board have been just as pervasive in computing: making a change often requires starting...
How is lightning initiated in thunderclouds? This is difficult to answer - how do you measure electric fields inside large, dangerously charged clouds? It was discovered, more or less by coincidence, that cosmic rays provide suitable probes to measure electric fields within thunderclouds. This surprising finding is published in Physical Review Letters on April 24th. The measurements were performed with the LOFAR radio telescope located in the Netherlands.
How is lightning initiated in thunderclouds? This is difficult to answer - how do you measure electric fields inside large, dangerously charged clouds? It was...
Max Planck researcher Buhalqem Mamtimin determines how much nitrogen oxide is released into the atmosphere from agriculturally used oases.
In order to make statements about current and future air pollution, scientists use models which simulate the Earth’s atmosphere. A lot of information such as...
23.04.2015 | Event News
23.04.2015 | Event News
13.04.2015 | Event News
24.04.2015 | Materials Sciences
24.04.2015 | Materials Sciences
24.04.2015 | Health and Medicine