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

November 29, 2012

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

Team finds link between backup immune defense, mutation seen in Crohn's disease

July 27, 2017
Genes that regulate a cellular recycling system called autophagy are commonly mutated in Crohn's disease patients, though the link between biological housekeeping and inflammatory bowel disease remained a mystery. Now, researchers ...

Co-infection with two common gut pathogens worsens malnutrition in mice

July 27, 2017
Two gut pathogens commonly found in malnourished children combine to worsen malnutrition and impair growth in laboratory mice, according to new research published in PLOS Pathogens.

Study sheds light on how body may detect early signs of cancer

July 26, 2017
Fresh insights into how cells detect damage to their DNA - a hallmark of cancer - could help explain how the body keeps disease in check.

How genetically engineered viruses develop into effective vaccines

July 26, 2017
Lentiviral vectors are virus particles that can be used as a vaccine to stimulate the immune system to fight against specific pathogens. The vectors are derived from HIV, rendered non-pathogenic, and then engineered to carry ...

Accounting for human immune diversity increases clinical relevance of fundamental immunological research

July 26, 2017
Mouse models have advanced our understanding of immune function and disease in many ways but they have failed to account for the natural diversity in human immune responses. As a result, insights gained in the lab may be ...

Study suggests same gut bacteria can trigger different immune responses depending on environment

July 24, 2017
(Medical Xpress)—A group of researchers affiliated with several institutions in the U.S. has found that one type of gut bacteria triggers different kinds of immune responses depending on the state of the environment they ...

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.