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
Moth takes advantage of defensive compounds in Physalis fruits
26.08.2016 | Max-Planck-Institut für chemische Ökologie
Designing ultrasound tools with Lego-like proteins
26.08.2016 | California Institute of Technology
Scientists and engineers striving to create the next machine-age marvel--whether it be a more aerodynamic rocket, a faster race car, or a higher-efficiency jet...
Waveguides are widely used for filtering, confining, guiding, coupling or splitting beams of visible light. However, creating waveguides that could do the same for X-rays has posed tremendous challenges in fabrication, so they are still only in an early stage of development.
In the latest issue of Acta Crystallographica Section A: Foundations and Advances , Sarah Hoffmann-Urlaub and Tim Salditt report the fabrication and testing of...
Electrochemists at TU Graz have managed to use monocrystalline semiconductor silicon as an active storage electrode in lithium batteries. This enables an integrated power supply to be made for microchips with a rechargeable battery.
Small electrical gadgets, such as mobile phones, tablets or notebooks, are indispensable accompaniments of everyday life. Integrated circuits in the interiors...
Recent findings indicating the possible discovery of a previously unknown subatomic particle may be evidence of a fifth fundamental force of nature, according...
A nanocrystalline material that rapidly makes white light out of blue light has been developed by KAUST researchers.
25.08.2016 | Event News
24.08.2016 | Event News
12.08.2016 | Event News
26.08.2016 | Health and Medicine
26.08.2016 | Earth Sciences
26.08.2016 | Life Sciences