Study shows how an important intestinal immune response controller works.


The intestines’ primary role is digestion, however, 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.  Now, a study from researchers led by the University of Bonn identifies a new regulatory mechanism where food components and environmental factors influence the immune system. The team state that their findings show how an important immune response controller works.  The opensource study is published in the journal Scientific Reports.

Previous studies show that 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, such as colitis or life-threatening septic shock. The Ah receptor has been shown to play an important role in this fine-tuning of the immune system in the intestines.  A large variety of substances can bind to the Ah receptor and trigger certain signal chains as they develop through the breakdown of food components, as well as environmental toxins.  The Ah receptor also has a counterpart, the Ah receptor repressor which partially inhibits the effect of the Ah receptor and together, both ensure there is an appropriate immune response. However, it is largely unknown how the Ah receptor repressor works.  The current study investigates how the interaction of the Ah receptor and its repressor works.

The current study utilised a mouse model whose gene for the Ah receptor repressor was replaced with one for a protein which fluoresce green, meaning that whenever the gene for the Ah receptor repressor is to become active, the fluorescent protein glows. Results show that the repressor in the intestinal immune cells is always particularly active when the Ah receptor is also operating at full speed. Data findings show that for a balanced immune response, both counterparts are necessary.

The lab explain that if the immune system mounts an excessive response, this can result in impending life-threatening septic shock through cardiovascular failure and organ damage. To counteract this they mutated the gene in mice for the Ah receptor repressor and the animals were then protected from such a hazardous shock. Results show, in contrast, a malfunction of the Ah receptor repressor as well as of the Ah receptor itself led to increased sensitivity for chronic bowel inflammation. Data findings show that both antagonists affect the production of immuno-stimulating substances, which include, interleukin-1 beta and interferon gamma; there is an appropriate immune response only if the Ah receptor and the Ah receptor repressor are in balance.

The team surmise that their study shows that food can have significant influence on the immune system. They go on to add that when vegetables contain many substances which bind to the Ah receptor and thus activate the associated repressor, this may stabilize the immune system in the intestines.  For the future, the researchers state that the degree to which the results in animals can be transferred to humans should be researched further.

Source: University of Bonn

 

AhRR/EGFP expression in the small intestine and in lymph nodes.  Immunofluorescence analysis of frozen sections of the SI, PP and colon of WT, AhRRE/+ and AhRRE/E mice counterstained with DAPI (bars: 200 μm).  Balancing intestinal and systemic inflammation through cell type-specific expression of the aryl hydrocarbon receptor repressor.  Förster et al 2016.

AhRR/EGFP expression in the small intestine and in lymph nodes. Immunofluorescence analysis of frozen sections of the SI, PP and colon of WT, AhRRE/+ and AhRRE/E mice counterstained with DAPI (bars: 200 μm). Balancing intestinal and systemic inflammation through cell type-specific expression of the aryl hydrocarbon receptor repressor. Förster et al 2016.

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