Schema of AhR-mediated development and exacerbation of atopic dermatitis. AhR is activated by air pollutants, such as traffic-derived particulate matter (pm2.5). Activated AhR induces the expression of artemin in keratinocytes, which induces hyper-innervation of the epidermis, resulting in hypersensitivity to itch. Subsequent scratching leads to barrier damage and increased penetration of antigens, which enhances sensitization that promotes a predisposition to other allergic diseases.Photo credit: Tohoku University
Researchers from Japan have identified part of the mechanism behind air pollution that causes some people to be made more vulnerable to atopic dermatitis.
“We have discovered that AhR, a transcription factor activated by air pollutants, causes hypersensitivity to itch, through the expression of neurotrophic factor artemin,” says Dr. Masayuki Yamamoto, a professor in the division of medical biochemistry, Tohoku University Graduate School of Medicine, in a press release. Dr. Yamamoto led the research team and was senior author on the paper. “Scratching makes things worse because the skin barrier gets disrupted and sensitization to antigens is enhanced. That’s why some people are predisposed to atopic dermatitis.”
In a paper published online in Nature Immunology (Nov. 21, 2016), the authors note that there is a well recognized correlation between air pollution and the prevalence and severity of atopic dermatitis, but that the underlying mechanism behind the link is not well understood.
The authors write that the transcription factor aryl hydrocarbon receptor (AhR) can be activated by organic components of air pollution. Through use of a mouse model, they identified rtn as a keratinocyte-specific AhR target gene. A product of that gene, the neurotrophic factor artemin, was responsible for epidermal hyper-innervation which led to hypersensitivity to pruritus in the model.
When looking at human subjects, they found that high levels of AhR activation and artemin expression were observed in atopic dermatitis patients but not in healthy individuals.
These findings may lead to new ways of controlling itch through inhibiting AhR or artemin, and through itch control reducing scratching, barrier disruption, and the atopic march.