Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Traffic Cops of the Immune System

30.11.2012
Molecule called IκBNS in charge of regulatory immune cell maturation

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 cop.


The figure shows the localization of IkBNS in the cell. IkBNS molecules (green) occur in dotted structures within the cell nucleus (blue). The function of these structures is, however, largely unknown.

HZI / Schmitz

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 IκBNS. Armed with this knowledge, the researchers hope to manipulate Tregs in order to either inhibit or activate the immune system. 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 chemical messengers. The regulatory cells 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: autoimmune diseases like rheumatoid arthritis or the chronic inflammatory bowel disease 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 donor organ.

But what it is exactly that makes immature immune cells 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 IκBNS contributes considerably to Treg development. The molecule promotes formation of the protein Foxp3, the Tregs' central feature. IκBNS influences the large NFκB family of transcription factors. 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 IκBNS’ central role in Treg maturation.

Essentially, these are cells capable of constraining inflammation – even though IκBNS 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 IκBNS’ central role in Treg development in mice that are missing this factor. Since cells that lack IκBNS 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 IκBNS is of interest from a medical perspective as well. On the one hand, it allows predicting diseases: If IκBNS is fraught with errors, this could trigger autoimmune disorders. On the other hand, one potential therapeutic goal might be "to manipulate IκBNS 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. "IκBNS stabilization could benefit autoimmune disease therapy. As far as infections or tumors are concerned, we would need to inhibit IκBNS to decrease the number of regulatory T cells. Of course, all that is still in the very distant future." But because IκBNS 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.

Original publication:
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 NFκB inhibitor IκBNS mediates regulatory T cell development by regulating Foxp3 induction
Immunity, 2012

The research group "Systems-oriented Immunology and Inflammation Research" explores the molecular processes that make immune cells tolerant to the body’s own tissues. This includes especially the cellular suicide program apoptosis.

The Helmholtz Centre for Infection Research
At the Helmholtz Centre for Infection Research in Braunschweig, scientists are studying microbial virulence factors, host-pathogen interactions and immunity. The goal is to develop strategies for the diagnosis, prevention and therapy of human infectious diseases.

The Otto von Guericke University Magdeburg:
One of the Otto von Guericke University Magdeburg Medical Faculty’s research emphases is "Immunology including molecular medicine relating to inflammation". The goal is to develop new therapeutic approaches and deliver them to the patient.

Dr. Jan Grabowski | Helmholtz-Zentrum
Further information:
http://www.uni-magdeburg.de
http://www.helmholtz-hzi.de/en
http://www.helmholtz-hzi.de/en/news_events/news/view/article/complete/traffic_cops_of_the_immune_system/

More articles from Life Sciences:

nachricht The birth of a new protein
20.10.2017 | University of Arizona

nachricht Building New Moss Factories
20.10.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Terahertz spectroscopy goes nano

20.10.2017 | Information Technology

Strange but true: Turning a material upside down can sometimes make it softer

20.10.2017 | Materials Sciences

NRL clarifies valley polarization for electronic and optoelectronic technologies

20.10.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>