An international team of researchers under the leadership of the LIMES Institute and the excellence cluster ImmunoSensation of the University of Bonn unraveled a new regulatory mechanism how food components and environmental factors influence the immune system. Various substances present in the intestines can bind to an important controller, the Ah receptor. This system is in turn regulated by the Ah receptor repressor and as a result, it influences the degree of the immune response. If the controller is not properly adjusted during bacterial infections, there can be life-threatening septic shock, for example. The results are now being published in the journal “Scientific Reports".
The intestines’ primary role is digestion but they must also achieve high performance around the clock defending against pathogens and environmental pollutants. This is because everything taken up with food ultimately ends up in the digestive tract.
“The intestines assume an important barrier function so that, to the greatest extent possible, no harmful organisms and substances are able to overcome this bastion,” says Prof. Dr. Irmgard Foerster, who is researching the connection between immunology and the environment at the Life and Medical Sciences (LIMES) Institute and in the excellence cluster ImmunoSensation of the University of Bonn.
The immune system in the intestines must be continually rebalanced. If its response is weak, pathogens and noxious substances have an easy job. If the immune reaction is excessive, there can be harmful inflammation – for example, colitis – to the point of life-threatening septic shock.
The “Ah receptor” (aryl hydrocarbon receptor) plays an important role in this fine-tuning of the immune system in the intestines. A receptor is a protein onto which certain molecules latch – similarly to how a key fits into a lock. A large variety of substances can bind to the Ah receptor and thus trigger certain signal chains: aromatic hydrocarbons as they develop, for example, through the breakdown of food components, but also environmental toxins such as dioxins.
Ah receptor and its repressor control the immune response together
The Ah receptor has a counterpart: the Ah receptor repressor which partially inhibits the effect of the Ah receptor. “Together, both ensure that there is an appropriate immune response,” says Dr. Heike Weighardt from Prof. Foerster’s team. Up to now, it was largely unknown how the Ah receptor repressor worked.
Together with scientists from the IUF Leibniz Research Institute for Environmental Medicine in Duesseldorf and the Waseda University in Tokyo (Japan), the researchers at the LIMES Institute and the excellence cluster ImmunoSensation of the University of Bonn have now researched how the interaction of the Ah receptor and its repressor works.
Using a mouse model, the team of scientists replaced the gene for the Ah receptor repressor with one for a protein which fluoresces green. “Whenever the gene for the Ah receptor repressor is to actually become active, the fluorescing protein glows,” says Oliver Schanz from the University of Bonn, one of the lead authors of the study.
It was demonstrated that the repressor in the intestinal immune cells is always particularly active when the Ah receptor is also operating at full speed. “Our data show that for a balanced immune response, both counterparts are necessary,” says Prof. Foerster.
The Ah receptor repressor increases the risk of septic shock
If the immune system mounts an excessive response, this can result in impending life-threatening septic shock through cardiovascular failure and organ damage. The team of researchers mutated the gene in mice for the Ah receptor repressor and the animals were then protected from such a hazardous shock.
By contrast, a malfunction of the Ah receptor repressor as well as of the Ah receptor itself led to increased sensitivity for chronic bowel inflammation. Both antagonists affect the production of immunostimulating substances, which include, for example, interleukin-1 beta or interferon gamma. “There is an appropriate immune response only if the Ah receptor and the Ah receptor repressor are in balance,” Dr. Weighardt concludes from these findings.
According to the scientists, the study shows that food can have a significant influence on the immune system. When vegetables – such as broccoli, for example – contain many substances which bind to the Ah receptor and thus activate the associated repressor, this may stabilize the immune system in the intestines. “The degree to which the results investigated in a model approach in animals can be transferred to humans must still be researched further,” says Prof. Foerster.
Publication: Balancing intestinal and systemic inflammation through cell type-specific expression of the aryl hydrocarbon receptor repressor, Scientific Reports, DOI: 10.1038/srep26091
Media contact information:
Prof. Dr. Irmgard Foerster
Immunology and Environment
ImmunoSensation Excellence Cluster
University of Bonn
Tel. ++49-(0)228-7362780 or 7362789
Johannes Seiler | idw - Informationsdienst Wissenschaft
A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
18.08.2017 | Life Sciences
18.08.2017 | Physics and Astronomy
18.08.2017 | Materials Sciences