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 Discovery of a fundamental limit to the evolution of the genetic code
03.05.2016 | Institute for Research in Biomedicine (IRB Barcelona)

nachricht Perfect imperfection
03.05.2016 | Christian-Albrechts-Universität zu Kiel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Nuclear Pores Captured on Film

Using an ultra fast-scanning atomic force microscope, a team of researchers from the University of Basel has filmed “living” nuclear pore complexes at work for the first time. Nuclear pores are molecular machines that control the traffic entering or exiting the cell nucleus. In their article published in Nature Nanotechnology, the researchers explain how the passage of unwanted molecules is prevented by rapidly moving molecular “tentacles” inside the pore.

Using high-speed AFM, Roderick Lim, Argovia Professor at the Biozentrum and the Swiss Nanoscience Institute of the University of Basel, has not only directly...

Im Focus: 2+1 is Not Always 3 - In the microworld unity is not always strength

If a person pushes a broken-down car alone, there is a certain effect. If another person helps, the result is the sum of their efforts. If two micro-particles are pushing another microparticle, however, the resulting effect may not necessarily be the sum their efforts. A recent study published in Nature Communications, measured this odd effect that scientists call “many body.”

In the microscopic world, where the modern miniaturized machines at the new frontiers of technology operate, as long as we are in the presence of two...

Im Focus: Tiny microbots that can clean up water

Researchers from the Max Planck Institute Stuttgart have developed self-propelled tiny ‘microbots’ that can remove lead or organic pollution from contaminated water.

Working with colleagues in Barcelona and Singapore, Samuel Sánchez’s group used graphene oxide to make their microscale motors, which are able to adsorb lead...

Im Focus: ORNL researchers discover new state of water molecule

Neutron scattering and computational modeling have revealed unique and unexpected behavior of water molecules under extreme confinement that is unmatched by any known gas, liquid or solid states.

In a paper published in Physical Review Letters, researchers at the Department of Energy's Oak Ridge National Laboratory describe a new tunneling state of...

Im Focus: Bionic Lightweight Design researchers of the Alfred Wegener Institute at Hannover Messe 2016

Honeycomb structures as the basic building block for industrial applications presented using holo pyramid

Researchers of the Alfred Wegener Institute (AWI) will introduce their latest developments in the field of bionic lightweight design at Hannover Messe from 25...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

The “AC21 International Forum 2016” is About to Begin

27.04.2016 | Event News

Soft switching combines efficiency and improved electro-magnetic compatibility

15.04.2016 | Event News

Grid-Supportive Buildings Give Boost to Renewable Energy Integration

12.04.2016 | Event News

 
Latest News

Quantum Logical Operations Realized with Single Photons

03.05.2016 | Physics and Astronomy

Discovery of a fundamental limit to the evolution of the genetic code

03.05.2016 | Life Sciences

Cavitation aggressive intensity greatly enhanced using pressure at bubble collapse region

03.05.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>