Anyone who suffers from neurodermatitis often experiences an itchy rash attack, especially during stressful phases. But why does the skin react so sensitively to stress? A study now shows which circuits of the nervous and immune systems are behind this. According to this, neurons in the skin activate certain immune cells, so-called eosinophils, which release inflammatory messengers. If the researchers suppressed this signaling pathway in mice, the influence of stress on skin health was reduced.
Around one in ten people in Germany suffers from neurodermatitis, also known as atopic dermatitis. During an attack, itchy eczema forms on the skin, which can severely limit the quality of life. “A well-recognized aggravating factor in atopic dermatitis is psychological stress, which can increase inflammation through complex interactions between the nervous system, the endocrine system and the immune system,” explains a team led by Jiahe Tian from Fudan University in Shanghai. However, it is still unclear which mechanisms cause stress to have this effect on the skin.
Stress as a trigger
Tian and his colleagues have now traced the underlying signaling pathways. To do this, they first evaluated data from 51 people with atopic dermatitis who had recorded their symptoms and stress levels and provided skin and blood samples. This showed that while most immune cells remained unaffected by the stress level, a certain group of immune cells, the so-called eosinophils, accumulated in the skin of stressed patients. This variant of white blood cells is known to release inflammatory messengers and can therefore worsen inflammation. “Based on these results, we came to the conclusion that there is a specific connection between the stress-related accumulation of eosinophilia and the severity of the skin inflammation,” report the researchers.
Tian and his team continued to follow this lead in experiments with mice. To do this, they first chemically triggered skin inflammation in mice, which is similar to eczema in humans. They then put the animals under stress in various ways, such as placing them unsecured on a high platform or fixing them in a narrow plastic tube. They then analyzed what influence this had on the inflamed skin, how the eosinophil levels changed and which nerve pathways were active.
Networking of nerve cells and the immune system
The result: Especially in the mice that were stressed by sitting at high altitudes, there was a massive release of stress hormones and, as a result, an accumulation of eosinophils in the skin – combined with an increased inflammatory reaction. Analyzes of the cells involved revealed that a subset of nerve cells in the skin, called prodynorphin-positive (Pdyn)+ noradrenergic sympathetic neurons, transmitted stress signals from the brain to the skin and activated eosinophils. If the researchers paralyzed the Pdyn+ nerve cells or removed the eosinophils, stress no longer caused inflammation to worsen in the mice. “These results suggest that stress-induced eosinophilia could be a potential biomarker for the severity of atopic dermatitis,” explain the researchers.
The findings could possibly also open up new therapeutic avenues. Neurodermatitis therapies that target eosinophils have been tested previously, but with limited success. However, in view of the new results, it is conceivable that certain groups of patients who suffer particularly from stress could benefit more from such treatment. Non-drug approaches would also be conceivable: “Integrating mental health interventions such as stress reduction, cognitive behavioral therapy or mindfulness into dermatological care could improve treatment outcomes in atopic dermatitis and other stress-sensitive skin diseases,” write Nicolas Gaudenzio and Lillan Basso from the University of Toulouse in France, who were not involved in the study, in an accompanying commentary.
Source: Jiahe Tian (Fudan University, Shanghai, China) et al., Science, doi: 10.1126/science.adv5974