Traffic cops of the immune system: Molecule called IKBNS in charge of regulatory immune cell maturation

November 29, 2012, Helmholtz Centre for Infection Research

A certain type of immune cell—the regulatory T cell, or Treg for short—is in charge of putting on the brakes on the immune response. In a way, this cell type might be considered the immune system's traffic cops.

Now, scientists at the Helmholtz Centre for Infection Research (HZI) have looked into the origin of Tregs and uncovered a central role played by the protein IkBNS. Armed with this knowledge, the researchers hope to manipulate Tregs in order to either inhibit or activate the . Biochemist Prof. Ingo Schmitz and his team have now published their findings in the scientific journal Immunity.

The immune system is a complex network of different types of cells and . The and other immune cells exist together in a delicate balance. Any disturbance of this balance could have serious consequences: If there are too many Tregs, the immune system might be "thwarted" and little would stand in the way of infections or tumors spreading throughout the body. By contrast, if there are too few Tregs, other immune cells could get out of control and attack the body's own tissues: like or the chronic ulcerative colitis may be a consequence. Tregs also play an important role following an organ transplant as they decide whether the body will accept or reject the .

But what it is exactly that makes immature choose the "police officer career" had eluded scientists. Schmitz and his team from the HZI, the Otto von Guericke University Magdeburg, the Charité Universitätsmedizin Berlin, the Harvard Medical School Boston, the TWINCORE in Hanover, the Eberhard Karls University Tübingen and the Heinrich Heine University Düsseldorf were now able to demonstrate that the transcription factor IkBNS contributes considerably to Treg development. The molecule promotes formation of the protein Foxp3, the Tregs' central feature. IkBNS influences the large NFkB family of . These signaling molecules trigger a number of different inflammatory responses elicited by the immune system. "It was therefore all the more surprising for us when we identified IkBNS' central role in Treg maturation. Essentially, these are cells capable of constraining inflammation – even though IkBNS in no way influences the function of regulatory T cells," explains Dr. Marc Schuster, one of Schmitz' colleagues at HZI and the article's first author. The researchers tested their hypothesis regarding IkBNS' central role in Treg development in mice that are missing this factor. Since cells that lack IkBNS do not "become cops," the immune system's effector cells are undamped and could trigger chronic inflammation of the intestine.

The results have confirmed that further research on IkBNS is of interest from a medical perspective as well. On the one hand, it allows predicting diseases: If IkBNS is fraught with errors, this could trigger autoimmune disorders. On the other hand, one potential therapeutic goal might be "to manipulate IkBNS in such a way that we can control the number of Tregs," explains Schmitz, who, in addition to his HZI research, also has a chair at the Otto von Guericke University Magdeburg. "IkBNS stabilization could benefit autoimmune disease therapy. As far as infections or tumors are concerned, we would need to inhibit IkBNS to decrease the number of regulatory T . Of course, all that is still in the very distant future." But because IkBNS also plays an important role in effector cell activation, an intervention might have unforeseen consequences. "This is a challenge you face with many different therapeutic targets," adds Schmitz.

Explore further: Self-regulation of the immune system suppresses defense against cancer

More information: Marc Schuster, Rainer Glauben, Carlos Plaza-Sirvent, Lisa Schreiber, Michaela Annemann, Stefan Floess, Anja A. Kühl, Linda K. Clayton, Tim Sparwasser, Klaus Schulze-Osthoff, Klaus Pfeffer, Jochen Huehn, Britta Siegmund, Ingo Schmitz The atypical NFkB inhibitor IkBNS mediates regulatory T cell development by regulating Foxp3 induction, Immunity, 2012

Related Stories

Self-regulation of the immune system suppresses defense against cancer

December 21, 2011
Regulatory T cells, which are part of the body's immune system, downregulate the activity of other immune cells, thus preventing the development of autoimmune diseases or allergies. Scientists at the German Cancer Research ...

New insight into immune tolerance furthers understanding of autoimmune disease

September 15, 2011
It is no easy task to preserve the delicate balance that allows us to maintain a strong immune system that can defend us from harmful pathogens, but that is sensitive enough to correctly identify and spare our own cells. ...

Regulatory immune cell diversity tempers autoimmunity in rheumatoid arthritis

May 8, 2012
Untangling the root cause of rheumatoid arthritis has been a difficult task for immunologists, as decades of research has pointed to multiple culprits in our immune system, with contradictory lines of evidence. Now, researchers ...

Researchers find regulatory T-cell clue to help prevent GVHD

October 31, 2011
Graft-versus-host disease (GVHD) is a serious risk in many kinds of cell transplants, including for stem cell transplants carried out when stem cells are partially depleted of conventional T cells, which play an important ...

Recommended for you

Immunosuppressive cells in newborns play important role in controlling inflammation in early life

January 15, 2018
New research led by The Wistar Institute, in collaboration with Sun Yat-sen University in China, has characterized the transitory presence of myeloid-derived suppressor cells (MDSCs) in mouse and human newborns, revealing ...

Memory loss from West Nile virus may be preventable

January 15, 2018
More than 10,000 people in the United States are living with memory loss and other persistent neurological problems that occur after West Nile virus infects the brain.

Mould discovery in lungs paves way for helping hard to treat asthma

January 15, 2018
A team at The University of Manchester have found that in a minority of patients they studied, a standard treatment for asthma—oral steroids—was associated with increased levels of the treatable mould Aspergillus in the ...

Fast food makes the immune system more aggressive in the long term

January 12, 2018
The immune system reacts similarly to a high fat and high calorie diet as to a bacterial infection. This is shown by a recent study led by the University of Bonn. Particularly disturbing: Unhealthy food seems to make the ...

Past exposures shape immune response in pediatric acute respiratory infections

January 12, 2018
Acute respiratory tract infections (ARTI) are the leading global cause of death in early childhood, according to the Centers for Disease Control and Prevention (CDC). Lower respiratory tract infections, including bronchiolitis ...

Scientists identify immune cells that keep gut fungi under control

January 11, 2018
Immune cells that process food and bacterial antigens in the intestines control the intestinal population of fungi, according to a new study from Weill Cornell Medicine scientists. Defects in the fungus-fighting abilities ...

0 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.