Why your psoriasis flares up in the same spots

Skin cells remember inflammation for life. Here’s why

By Claire Cameron edited by Jeanna Bryner

Skin holds memories. The scar from a childhood fall and the freckle from a summer past are more than just marks; they are evidence of skin’s ability to store life’s moments. Researchers have now discovered that skin truly remembers, particularly for those affected by inflammatory conditions like psoriasis, which repeatedly flare up in the same locations. Scientists believe they have uncovered the reason behind this phenomenon.

A recent study in Science, conducted with mice, reveals how skin cells pass on gene expression patterns with each regeneration. The study demonstrates that not only do skin cells retain the structural memory of their DNA, but they also inherit epigenetic marks—chemical alterations that can switch genes on or off or modulate their expression.

“It was known that stem cells could alter their behavior and remember past states, but the role of epigenetic mechanisms was unclear,” explains Shruti Naik, a molecular biologist at the University of Maryland, College Park, who has collaborated with the study’s senior author, Elaine Fuchs. Naik was not part of the current research. “This paper convincingly shows that DNA marking enables stem cells to behave differently in subsequent generations.”

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The memory of skin stem cells can be advantageous; for instance, a previous cut will heal faster if it occurs again because the skin cells remember the injury. However, this memory can complicate conditions like psoriasis, where the tissue’s sensitivity to triggers such as stress can lead to persistent inflammation.

“Your DNA can remember past injuries much longer than we previously thought,” notes Dana Pe’er, a co-author of the study and head of the Computational and Systems Biology Program at the Sloan Kettering Institute. “It’s a double-edged sword.”

For their research, the team employed an artificial intelligence model to pinpoint specific genetic sequences in mice that contribute to long-term skin stem cell memory. They achieved this by analyzing DNA behavior in response to an injury—in this case, a small incision on the mice’s back. Pe’er describes the AI findings as “opening a black box,” which they then confirmed through further investigation.

Although mice and humans differ, the biological processes identified are conserved across species, suggesting potential relevance to human biology, explains Naik.

Pe’er adds that this discovery paves the way for human studies, though they will be more challenging. Human skin cells regenerate over weeks or months, and chronic diseases can persist for a lifetime, unlike in mice, where regeneration occurs over days and diseases last months or a few years.

Naik emphasizes the growing evidence that inflammation can reshape the body’s biological path. “The field is moving towards understanding how life experiences alter our fundamental biology and what that means for disease onset in our current lifestyles.”

“Imagine if we could erase that imprint—reverse the damage—and essentially control our health,” she suggests.

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