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.
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.
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
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 | Source: Helmholtz-Zentrum
Further information: www.uni-magdeburg.de
Further Reports about: autoimmune disease > COPS > Foxp3 > Helmholtz > HZI > IêBNS > immune cell > Immune cell activation > immune system > Immunology > Infection > inflammatory response > Medical Wellness > molecular process > signaling molecule > T cells > Traffic > transcription factor
More articles from Life Sciences:
Molecular snapshot of the plant immune system’s signal box
11.12.2013 | Max Planck Institute for Plant Breeding Research, Köln
Successful Teamwork: Unusual fungal metabolites with antitumor activity discovered by crowdsourcing
11.12.2013 | Angewandte Chemie International Edition
The molecular architecture of three key proteins and their complexes reveals how plants fine-tune their immune response to pathogens
Plants rarely get sick in their natural environment. When the threat of infection arises, a quick decision is made about the necessary countermeasures. The course is set by a protein which forms complexes with its partner proteins for this purpose.
Jane Parker from the Max Planck Institute for Plant Breeding ...
Researchers studying speciation of butterfly orchids on the Azores have been startled to discover that the answer to a long-debated question "Do the islands support one species or two species?" is actually "three species".
Hochstetter's Butterfly-orchid, newly recognized following application of a battery of scientific techniques and reveling in a complex taxonomic history worthy of Sherlock Holmes, is arguably Europe's rarest orchid species. Under threat in its mountain-top retreat, the orchid urgently requires conservation recognition.
A lavishly illustrated publication, titled "Systematic revision of Platanthera in ...
Researchers from Brown University and the University of Hawaii have found some mineralogical surprises in the Moon's largest impact crater.
Data from the Moon Mineralogy Mapper that flew aboard India's Chandrayaan-1 lunar orbiter shows a diverse mineralogy in the subsurface of the giant South Pole Aitken basin.
The differing mineral signatures could be reflective of the minerals dredged up at the time of the giant impact 4 billion years ago, ...
In power electronics systems bonded connections create the central electrical connections between adjoining surfaces.
The quality of these bonded connections is one of the main factors that determines the reliability and availability of drive systems in electric vehicles, and hence constitutes a major design challenge for German auto manufacturers aiming to electrify their vehicles.
Now the partners participating in the RoBE (Robust Bonds in ...
International team of scientists develops new feedback method for optimizing the laser pulse shapes used in the control of chemical reactions
In many ways, traditional chemical synthesis is similar to cooking. To alter the final product, you can change the ingredients or their ratio, change the method of mixing ingredients, or change the temperature or pressure of the environment of the ingredients.
Like an accomplished chef, chemists have become very skilled ...
11.12.2013 | Information Technology
11.12.2013 | Life Sciences
11.12.2013 | Agricultural and Forestry Science
11.12.2013 | Event News
10.12.2013 | Event News
05.12.2013 | Event News