01:16am Monday 14 October 2019

Why growing up on a farm protects against asthma and allergies

Bart and Hamida, what exactly has your research revealed?
Bart: Simply put, we have revealed a causal relationship between the exposure to farm dust and protection against asthma and allergies. In our Immunity paper, we had already revealed that the structural cells that make up the lining of the lung play an important role in allergic airway inflammation. The following paper, which appeared in Science, showed why farm dust makes the mucous membrane inside the respiratory tracts react less severely to allergens such as house dust mite.

How was the research conducted?
Hamida: We exposed mice to farm dust extract from Germany and Switzerland. Our tests revealed that these mice were fully protected against house dust mite allergy, the most common cause for allergies in humans.

Did you find out why this is the case?
Hamida: The effect is triggered by the A20 protein, which the body produces upon contact with farm dust. When we inactivate the A20 protein in the mucous membrane of the lungs, farm dust is no longer able to reduce an allergic or asthmatic reaction. Surprisingly, this protein doesn’t actually affect the immune system but the structural cells in the lung. When these cells are exposed to farm dust, they get ‘numbed’ or ‘cooled’, which causes them to stop recognizing common allergens later in life.

Did patient tests reveal the same results?
Bart: Yes. Patient tests showed that people suffering from allergies and asthma have a deficiency in the protective protein A20. It explains why they react to allergens so severely. We also assessed a test group of 2,000 children growing up on farms, and found that most of them are protected. Those who are not protected and still develop allergies have a genetic variant of the A20 gene which causes the A20 protein to malfunction.

So exactly which active substances in farm dust are responsible for the protection?
Hamida: That’s what we are trying to find out now. We already suspect that part of the answer lies in the endotoxines, fragments of dying bacteria found in farm dust and cow manure. But there are very likely other contributing substances as well.

How does this research open new perspectives in medicine research?
Bart: This is undoubtedly a major step forward towards the development of an asthma vaccine. Once we can identify the active substances in farm dust, the development of a preventive medicine may be the next step.

Bart and Hamida have a shared a long academic track record. “Our first collaboration was about 13 years ago, during postdoctoral research in Rotterdam”, Bart confirms. “We’ve been working together ever since and it even led to our own lab, which is focused on unraveling the functions of lung dendritic cells and epithelial cells in asthma and respiratory viral infections.”

What makes both researchers such a good combination?
“I think it’s because we’re very complementary”, Hamida says. “As a pulmonologist and a doctor, Bart has a more clinical approach towards immunity, while I am more focused on the cellular level. Combining both angles has contributed tremendously to our findings in the past years.”

Schuijs et al., Science. 2015
Coquet et al., Immunity. 2015

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