Researchers have discovered how the body regulates and prevents constant skin inflammation, a finding they say could completely transform how doctors think about skin immune regulation and how skin inflammation and dermatological conditions are treated.
A new study, conducted by scientists at University of California San Diego School of Medicine, has identified two enzymes that are responsible for protecting the skin and body’s overall health from microbial intruders. The enzymes – known as histone deacetylases (HDACs) – inhibit the inflammatory responses in the skin.
The body is constantly exposed to various environmental actors including viruses, bacteria, and fungi, however, most of these organisms do not provoke a response from our skin which monitors and protects the body from external dangers. Before this study, which has been published in Science Immunology, it was unclear why the skin is not constantly inflamed.
Skin inflammation
The researchers say the potential mechanism for how the environment can interact and alter cell function is through epigenetic control of gene expression. Within the skin cells, proteins called toll-like receptors (TLRs) allow the cells to sense potential dangers. These act as a warning system that triggers an inflammatory response to threats in most organs, however, in skin cells, the two identified HDAC enzymes – HDAC8 and HDAC9 – inhibit the inflammatory response.
Richard Gallo, MD, PhD, Ima Gigli Distinguished Professor of Dermatology and chair of the Department of Dermatology at UC San Diego School of Medicine, commented: “We have figured out why we tolerate certain microbes living on our skin, while the same bacteria would make us very sick if exposed elsewhere in the body. In our research, we identified enzymes that act on the chromosome of specific skin cells that provide immune tolerance by the skin.
“Without these enzymes telling our cells to ignore certain bacteria, we’d have a constant rash on our skin.”
“This is one of the first demonstrations of how the microbiome can interact with epigenetic factors in the skin and modulate the skin’s behaviour through the inflammatory response,” said George Sen, PhD, associate professor of dermatology and cellular and molecular medicine at UC San Diego School of Medicine. “Whatever environment we’re facing can change a person’s specific response to it. Since this epigenetic change is reversible, unlike alterations to our DNA, we can potentially control our skin inflammatory response through targeting of these enzymes.”
Future treatments for skin conditions
The research, initially conducted in mouse models in which HDAC8 and HDAC9 had been genetically knocked out, found that the mice’s skin could not tolerate microbial or viral exposures. This resulted in a heightened immune reaction. The team then reproduced the findings with human cells in a culture dish.
Gallo highlighted that work could change how doctors treat certain types of skin inflammation or other dermatologic conditions.
“This is a completely new way to think about skin immune regulation. Through alterations in HDAC activity, we’ve provided a possible way to explore and quiet down unnecessary inflammation by working with skin cells themselves. In the future, drugs designed to turn these enzymes on or off could help treat skin disease as an alternative to antibiotics.”
