Owning A Dog May Protect Against Eczema

About 100 million adults and 100 million children worldwide have the red, flaky, itchy skin of the most common form of eczema, atopic dermatitis, according to the NIH. The condition stems from a misdirected immune response to a substance – an allergen – that does not actually present a threat. Although the exact causes of eczema aren’t well understood, a new study points to an unexpected protective factor: owning a dog.

Allergies like eczema arise from complex interactions of genetic and environmental factors. The new report, in the journal Allergy, is from an international team. The investigators pooled and analyzed the results of many studies to identify possible contributing factors to developing eczema.

Genes Versus Environmental Factors
Eczema is a “complex trait,” which means that environmental factors and genetic tendencies contribute to developing the condition. Because genes encode proteins, analyzing the proteins at the site of action – skin – can reflect what’s going on at the DNA level. For example, a large skin protein called filaggrin triggers eczema when it’s present in half the normal amount. At full strength, filaggrin breaks down and releases its constituent amino acids, which provide moisture, soothing skin and keeping out irritants, pathogens, and allergens. But with too little filaggrin, skin cracks. Allergens penetrate deeper into the skin layers, where they activate the immune system’s dendritic cells, signaling the inflammation that lies behind eczema.

Eczema affects about 20% of children and 10% of adults in high-income countries. Although there’s a genetic tendency, the observation that it’s become more prevalent in these parts of the world over the past three decades points to important environmental factors as well. And that means prevention is possible – we have greater control over environmental factors than inherited ones.

To identify the gene–environment interactions behind eczema, the researchers analyzed data from 16 European studies. They zeroed in on 24 sites in the genome, as well as 18 “early-life environmental factors” during the mother’s pregnancy and the child’s first year of life, that are associated with developing the skin condition. The association held up when considering ten additional studies and modeling eczema in skin cells growing in the lab.

Seven possible environmental factors associated with eczema emerged from analysis of an initial 25,339 individuals: taking antibiotics, owning a cat, owning a dog, breastfeeding, having an older sibling, smoking, and hygiene habits.

Repeating the analysis on an additional 254,532 people singled out exposure to a dog as being associated with not having eczema. And the earlier the exposure to canines, the greater the apparent protection.

How Can Dogs Protect Against Eczema?
When scientists accrue evidence to support or refute an hypothesis, the next step is to hypothesize again – at the molecular level, how does a canine keep eczema at bay? What is the mechanism?

It turns out that the dog owners in the studies share a specific DNA sequence as part of chromosome 5 near a key immune system gene that triggers inflammation. That gene encodes the interleukin-7 receptor (IL7R) protein. People with two copies of the DNA sequence indeed make less IL-7R in skin cells, setting up the vulnerability to eczema – yet somehow, owning a dog mitigates the effect.

Backing up the findings were laboratory tests that showed that human skin cells with the genetic variant, when given molecular signals from a dog that could trigger allergy, instead suppressed inflammation in skin.

The studies taken together suggest that targeting IL-7R could treat, or perhaps even prevent, eczema – although getting a dog might be easier!

Said investigator Marie Standl, from Helmholtz Munich, “This study sheds light on why some children develop eczema in response to environmental exposures while others don’t. Not every preventive measure works for everyone – and that’s precisely why gene–environment studies are crucial. They help us move toward more personalized, effective prevention strategies.”

CODA
A huge limitation of the otherwise elegant study is that the data came from a white, European population. It will take a few more years and more realistic investigations for population databases to better reflect the reality of human genetic diversity – that People of the Global Majority – non-whites – constitute 85 percent of the human population.