Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Sensitive balance in the immune system


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".

Inflammed lung tissue with immune cells that have migrated into the lungs. Their nuclei are stained blue. HZI/Pils

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.

Original publication
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.

Weitere Informationen: - This press release on

Dr. Birgit Manno | Helmholtz-Zentrum

More articles from Life Sciences:

nachricht Molecular trigger for Cerebral Cavernous Malformation identified
26.11.2015 | EMBO - excellence in life sciences

nachricht Peering into cell structures where neurodiseases emerge
26.11.2015 | University of Delaware

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Climate study finds evidence of global shift in the 1980s

Planet Earth experienced a global climate shift in the late 1980s on an unprecedented scale, fuelled by anthropogenic warming and a volcanic eruption, according to new research published this week.

Scientists say that a major step change, or ‘regime shift’, in the Earth’s biophysical systems, from the upper atmosphere to the depths of the ocean and from...

Im Focus: Innovative Photovoltaics – from the Lab to the Façade

Fraunhofer ISE Demonstrates New Cell and Module Technologies on its Outer Building Façade

The Fraunhofer Institute for Solar Energy Systems ISE has installed 70 photovoltaic modules on the outer façade of one of its lab buildings. The modules were...

Im Focus: Lactate for Brain Energy

Nerve cells cover their high energy demand with glucose and lactate. Scientists of the University of Zurich now provide new support for this. They show for the first time in the intact mouse brain evidence for an exchange of lactate between different brain cells. With this study they were able to confirm a 20-year old hypothesis.

In comparison to other organs, the human brain has the highest energy requirements. The supply of energy for nerve cells and the particular role of lactic acid...

Im Focus: Laser process simulation available as app for first time

In laser material processing, the simulation of processes has made great strides over the past few years. Today, the software can predict relatively well what will happen on the workpiece. Unfortunately, it is also highly complex and requires a lot of computing time. Thanks to clever simplification, experts from Fraunhofer ILT are now able to offer the first-ever simulation software that calculates processes in real time and also runs on tablet computers and smartphones. The fast software enables users to do without expensive experiments and to find optimum process parameters even more effectively.

Before now, the reliable simulation of laser processes was a job for experts. Armed with sophisticated software packages and after many hours on computer...

Im Focus: Quantum Simulation: A Better Understanding of Magnetism

Heidelberg physicists use ultracold atoms to imitate the behaviour of electrons in a solid

Researchers at Heidelberg University have devised a new way to study the phenomenon of magnetism. Using ultracold atoms at near absolute zero, they prepared a...

All Focus news of the innovation-report >>>



Event News

Fraunhofer’s Urban Futures Conference: 2 days in the city of the future

25.11.2015 | Event News

Gluten oder nicht Gluten? Überempfindlichkeit auf Weizen kann unterschiedliche Ursachen haben

17.11.2015 | Event News

Art Collection Deutsche Börse zeigt Ausstellung „Traces of Disorder“

21.10.2015 | Event News

Latest News

Using sphere packing models to explain the structure of forests

26.11.2015 | Ecology, The Environment and Conservation

Dimensionality transition in a newly created material

26.11.2015 | Materials Sciences

Revealing glacier flow with animated satellite images

26.11.2015 | Earth Sciences

More VideoLinks >>>