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Discovery helps explain psoriasis inflammation

By Melissa Leavitt

Researchers have identified a protein involved in inflammation that could point the way toward a new treatment for psoriasis.

A recent study found that activating the protein, called an aryl hydrocarbon receptor (AhR), reduced inflammation in the skin of people with psoriasis. AhR is a transcription factor, which is a protein that binds to DNA and regulates the expression of certain genes.

Scientists already knew that AhR helped control the body's response to toxins, such as environmental pollutants, or toxins produced by the body. This study, published in the June issue of Immunity, shows that AhR can also help reduce inflammatory responses, said Paola Di Meglio, a lead author of the study.

The findings also suggest, said Di Meglio, that something has disrupted the anti-inflammatory effects of AhR in people with psoriasis.

Scientists know that psoriasis is caused by a combination of genetic mutations and environmental influences, such as stress, injury or infection. However, scientists don't fully understand how environmental risk factors trigger psoriasis.

To better understand these mechanisms, the researchers zeroed in on AhR to study how genes and the environment work together in the development of psoriasis.

First, they identified which of the genes involved in psoriasis were controlled by AhR. Then they analyzed what happened to these genes when AhR was activated.

It turns out that "turning on" AhR reduced the expression of these genes, and had an anti-inflammatory effect. And the opposite was also true: Blocking AhR increased inflammation.

"It is reasonable to hypothesize, based on our data, that in psoriasis there is an impaired activation of the AhR pathway," said Di Meglio. This finding opens up the possibility of developing new therapies for psoriasis that target the AhR pathway.

These treatments may offer an alternative to currently available therapies, such as biologic drugs, which, said Di Meglio, are "highly effective," but "exclusively aimed at suppressing inflammation." Instead, AhR-based therapies, which could also be combined with biologics, would aim to restore a normal process in the body that is "somehow altered in psoriasis," she explained.

Any therapy involving the AhR pathway would "require a careful design, as the pathway needs to be tightly regulated," she said. Di Meglio cautions that simply increasing activation of AhR could have the same damaging effects as increasing the amount of toxins in the body.

The development of these therapies could still be far off, according to Di Meglio. Before they can be explored, scientists still need to determine how and why AhR activation is impaired in people with psoriasis, and which patients could be good candidates for this type of treatment, she said.

 


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