Why Does Psoriasis Occurs On The Same Spot?

The skin remembers. The skin don't forget. That scar above your eye from when you fell at age 6. That freckle from the summer you turned 13. Our skin is a repository of moments from our lives, and now scientists have found it really does remember.

For people with inflammatory skin conditions such as psoriasis, the skin’s memory manifests in flare-ups in the same spots over and over. And now scientists think they know precisely why this happens.

In a new study in mice published on 26 March in Science, researchers showed how skin cells inherit patterns of gene expression every time they regenerate. The team found not only that successive generations of skin cells maintain the memory of their DNA’s structure but also that the cells inherit chemical modifications to the DNA called epigenetic marks, which can turn on or off, or turn certain genes up and down in a process called gene expression.

"People knew that stem cells had the ability to change their behavior and remember, but they didn’t know if it was through this epigenetic mechanism," says Shruti Naik, a molecular biologist at the University of Maryland, College Park, who has previously worked with the study’s senior author, Elaine Fuchs, but was not involved in the new research. "And I think what this paper does is definitively demonstrate that it's through marking of DNA ... that it allows that stem cell to now behave differently moving forward."

Skin stem cell memory can be beneficial: if you get a cut, for example, your skin will heal faster in that place if it is injured again because the cells remember the experience. But that becomes problematic in conditions like psoriasis, for which the memory of a flare-up can make the tissue overly sensitive to environmental triggers such as stress, leading to chronic inflammation.

"Your DNA can remember, far longer than we appreciated, a past injury," says Dana Pe’er, a co-author of the study and chair of the Computational and Systems Biology Program at the Sloan Kettering Institute. "It’s a double-edged sword."

For the study, the researchers used an artificial intelligence model to help identify specific genetic sequences in mice that drive skin stem cell memory over the long term. They did this by asking the model to look at how regions of the cells’ DNA behaved at different time points before and after an injury—in this case, a punch biopsy, which involved making a very small incision on the mice’s back. The AI findings were like “opening a black box” that the researchers then further verified, Pe’er says.

And while mice are not humans, the biology the team has identified is highly conserved across animals, Naik explains, and this suggests the finding may have some applicability to humans.

The new research opens the door to testing it in humans, Pe’er adds. But these studies will be more difficult because, whereas mouse skin cells regenerate on timescales of days and chronic disease is measured in months or perhaps one to two years, human skin cells do so on the order of several weeks or months, and chronic disease can be lifelong.