Lung protein key in allergies

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People who grow up on farms - especially dairy farms - have way fewer allergy and asthma problems than the rest of us. 

 Now one research team thinks they've brought science closer to understanding why. 

In a study published in Science, researchers report that they were able to pinpoint one possible mechanism for the allergy protection in mice they studied. Surprisingly, the protein that they fingered as the likely allergy-preventer doesn't actually affect the immune system - it affects the structural cells that make up the lining of the lung. 

The research is related to something called the hygiene hypothesis, where a lack of exposure to microbes as a tyke leads to more allergy and asthma. It's what leads microbiologists to say that the best thing you can do for your kid is roll them around on the floor of the subway . That may indeed be true (as long as you roll very, very carefully!) but there's increasing evidence that farms have the best germs for preventing respiratory problems and allergic reactions later in life. 

One study found that just 25 percent of children living on Swiss farms reacted to common allergens like dust mites, pollen, animals and mould, while 45 percent of children in the general population reacted. 

And among Amish children - who obviously have some of the farmiest of farm lives, though other factors may also be at play - reactions fall to a shocking eight percent or less. 

It's still not totally clear what's behind this amazing allergy protection, but many scientists believe that the bacteria native to farms, especially ones that house livestock, may trigger something in children who live nearby. 

The researchers behind the latest study had previously found that the epithelial cells of the lungs are important in the development of allergy responses. 

“How does your body react the first time you inhale an allergen? The first cells that recognise the allergen are not so much the cells of the immune system, but the structural cells that make up the inside of the lungs,” Bart Lambrecht of Ghent University, who co-led the study with Hamida Hammad, said. 

So they wanted to see how this farm effect might be visible in the lungs themselves. 

In their experiment, Lambrecht and Hammad induced dust mite allergies in mice, then showed that exposure to dust from a dairy farm made early in life made them immune. 

Then, they studied the mechanism that was protecting the mice, making their mucous membranes less likely to react to the allergens. They found a protein called A20, which the mice were producing when exposed to the farm dust. When the researchers knocked out the A20 in their subjects' lungs, the farm dust stopped protecting them from allergic reactions. 

A test in mice can't definitively provide answers on human health. But the research team did go one step further - they tested 2 000 children who lived on farms, and they found that those who suffered from allergies in spite of their upbringing had a mutation on the gene related to A20, causing the protein to malfunction.
“A20 was not a coincidence, it was really necessary,” Lambrecht said. “This is linking, showing a cause and effect link, between exposure to farm dust and fewer allergies. I think our study is a big step forward.” 

While there are almost certainly other factors at play in allergy development and prevention, Lambrecht and his colleagues hope that the cells of the lung itself will get more attention in research. This could be a sign, he said, that allergy and asthma vaccines need to be administered by aerosol instead of injection in order to truly be effective. And it may mean that epidemiologists need to think twice before focusing on blood samples alone in their allergy studies. 

“The study opens an new area of investigation in our long quest to understand the hygiene hypothesis, which is the complex interaction of farm exposures and their impact on the function of structural cells of the airway,” said Mark Holbreich, a physician who studies the hygiene hypothesis but was not involved in the new research. 

But while A20 is a fascinating new piece of the puzzle, it's unlikely to put an end to allergies as we know them. 

“We know from many studies that there appear to be multiple factors that contribute to protection,” Holbreich said. “This article adds to our expanding knowledge yet we are still far from developing a means for the primary prevention of allergies and asthma.” 
 Washington Post