Skin cells remember previous injury

18 October 2017
Posted by Chris Smith.

Skin cells can remember previous injuries and respond much more rapidly if the same patch tissue is injured again, a new study has shown. The work may help to inspire new treatments for skin conditions like eczema, psoriasis and even skin cancer.

When tissues are damaged a state known as inflammation ensues. An ingress of immune cells, a boost in blood flow to the injured area, and increased rates of cell growth together enable rapid repairs to be made, restoring the tissue to a healthy, intact state. But now scientists have discovered an additional facet to this repair process: prior experience.

Working with mice, Rockefeller University researcher Shruti Naik and her colleagues have found that, following an earlier injury, stem cells within the damaged patch of skin retain a memory of the earlier insult. This enables them to swing into action far more rapidly if a subsequent injury is sustained in the same place.

In the team's study, published this week in Nature, mice were subjected to small injuries placed in patches of previously-traumatised skin. These injuries healed 2.5 times faster than similar injuries sustained elsewhere on the body, or in healthy never-before-injured control animals. 

The researchers ruled out immune cells as a cause of the memory effect by repeating the experiments in mice unable to produce key populations of white blood cells. Although these animals did heal slightly more slowly overall, because immune cells play a key role in orchestrating the inflammatory response, damage to previously-injured skin still healed at twice the rate compared with skin that had not received a prior injury.

Instead, skin stem cells, the team have found, appear to be able to harbour a genetic memory of an earlier insult, which primes and sensitises specific genes required to kickstart a rapid reaction to a subsequent injury. 

This is achieved by unwinding or "opening up" segments of the stem cell's DNA, exposing the genes in these regions of the genome so that they can respond quickly to any rise in inflammatory signals around the cell. 

As long as 180 days after a skin injury been sustained, more than 2000 DNA sites remained opened up like this in stem cells at the injury site. And when a fresh injury was sustained, the majority of the first genes to be switched on in the affected cells were from these primed regions.

Naik and her colleagues speculate that this inflammatory memory enables skin to guard against the dermatological equivalent of a double lightning strike: anticipating subsequent damage means that repair machinery can be brought to bear more rapidly. "These changes endow [skin stem cells] with the ability to accelerate their response to subsequent stressors," say the team. 

Beneficial as that sounds, there is a sting in the tail. "Genetic alterations that mobilize stem cells more rapidly are often associated not only with accelerated wound repair, but also with increased susceptibility to cancer," they suggest, pointing out that processes that prime cells for growth can also lead to malignancies. 

The same memory effects may also contribute to autoimmune skin diseases, like psoriasis, and allergic conditions like eczema. If so, the mechanism uncovered by the Rockefeller team may provide exciting new opportunities for developing novel therapies for both diseases.

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