Sensitive balance in the immune system

The image shows inflammed lung tissue with immune cells that have migrated into the lungs. Their nuclei are stained blue. Credit: Helmholtz Association of German Research Centres

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 . 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 , 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 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 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.

More information: 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

add to favorites email to friend print save as pdf

Related Stories

Live and let die: Protein prevents immune cell suicide

May 31, 2013

A protein called c-FLIP-R is critical to immune cell survival: If this molecule is missing, the cells kill themselves – and are thus no longer able to perform their job fighting off invaders. Now, scientists ...

Immune cell death defects linked to autoimmune diseases

Jan 23, 2013

Melbourne researchers have discovered that the death of immune system cells is an important safeguard against the development of diseases such as type 1 diabetes, rheumatoid arthritis and lupus, which occur ...

B-cells aggravate autoimmune diseases

Mar 04, 2014

Scientists in Freiburg may have discovered a fundamental aggravating factor in autoimmune diseases. If B-lymphocytes lack the protein PTP1B, the cells will become hyperactive for stimulatory signals and can ...

Recommended for you

Could trophoblasts be the immune cells of pregnancy?

Dec 18, 2014

Trophoblasts, cells that form an outer layer around a fertilized egg and develop into the major part of the placenta, have now been shown to respond to inflammatory danger signals, researchers from Norwegian University of ...

Moms of food-allergic kids need dietician's support

Dec 18, 2014

Discovering your child has a severe food allergy can be a terrible shock. Even more stressful can be determining what foods your child can and cannot eat, and constructing a new diet which might eliminate entire categories ...

Multiple allergic reactions traced to single protein

Dec 17, 2014

Johns Hopkins and University of Alberta researchers have identified a single protein as the root of painful and dangerous allergic reactions to a range of medications and other substances. If a new drug can ...

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.