Stem cells have a memory of past inflammations

Scientists from Rockefeller University, USA, found that skin stem cells permanently “memorize” wounds or other traumas that cause inflammation in order to heal such damage more quickly. The results of a study, published October 18, 2017 in Nature, can help in the research and treatment of psoriasis, as well as other inflammatory diseases.

Scientists have determined that the primary inflammation sensitizes the stem cells of the outer layer of the skin, and in the future they react more quickly in a similar situation.

This study shows for the first time that the skin is capable of forming memories of an inflammatory response. This discovery, says lead author Elaine Fuchs, can be an important stage for better understanding and treatment of a number of diseases.

“By enhancing responsiveness to inflammation, these memories help the skin maintain its integrity, a feature that is beneficial in healing wounds after an injury,” says Fuchs, Professor of Mammalian Cell Biology and Development at The Rockefeller University. “This memory may also have detrimental effects, however, such as contributing to the relapse of certain inflammatory disorders such as psoriasis.”

The skin is quickly inflamed: from sunburn, attacked by microbes, cuts, it swells, becomes red and painful – it is the reaction of the body, which seeks to halt the damage and initiate repair.

It has long been known that the immune system maintains a memory of inflammation in order to respond faster to recurrent infections. But scientists in the Fuchs’ lab suggested that other types of long-lived cells might similarly remember inflammation. The most logical thing was to start searching with the study of the skin: as a protective barrier to the body, it endures frequent assaults.

It soon became apparent that most of the cells in the skin’s outermost layer such, the epithelium, do not live long enough to form such memories. Throughout their existence, they migrate through the epithelium and eventually slough off. However, in the deeper layers of the epithelium there are stem cells responsible for its constant renewal. These stem cells remain in their place after a long time after inflammation, and as the team found, this experience changes them.

In experiments with mice, Shruti Naik, a postdoc, and Samantha B. Larsen, a graduate student, showed that the wounds healed more than twice as fast in the skin that had already experienced irritation than in the skin that had never been injured. Even if the experience of primary inflammation had happened as long as six months earlier, which is equal of about 15 years for a human.

Healing sped up, the team determined, due to faster migration of “inflammation- experienced” stem cells for healing of lesions

.In other experiments, the researchers found the main mechanisms that rewire these cells. They showed that inflammation triggers a process that physically opens up individual patches in the cell’s chromosomes, making certain genes available for activation. Some of these sites remain open for a long time after the restoration of the skin, allowing the genes to activate more quickly in response to repeated trauma.

A special role in this process is played by the Aim2 gene, which encodes a protein that is sensitive to damage. Primary inflammation stimulates a prolonged increase in its expression. Repeated trauma quickly activates the protein, resulting in an inflammation signal that increases the ability of stem cells to migrate to the wound.

From time to time inflammation can run amok, as happens in autoimmune diseases, such as psoriasis, which is characterized by the appearance of scaly, red patches, often occurring in the same spot. New research suggests that the skin itself could contribute to this recurring reaction.

However, in fact, the consequences can manifest themselves much deeper than the skin. The findings of the research group also relate to inflammatory diseases of other parts of the body, such as the linings of the gut, which, like the skin, are replenished by epithelial stem cells.

“Inflammatory diseases have long been blamed on immune cells that turn against the body. However, that is clearly not the only cause: Stem cells may also be important contributors,” – Larsen says.

“A better understanding of how inflammation affects stem cells and other components of tissue will revolutionize our understanding of many diseases, including cancer, and likely lead to novel therapies,” – Naik says.