Researchers are identifying new molecular mechanisms in skin inflammation

Different skin causes such as inflammation in atopic dermatitis (AD or neurodermatitis) and psoriasis are for different reasons such as genetic predisposition, stress or allergens.

These skin diseases that often appear as a result of biochemical scientists have an immune system that is disturbed, despite the apparent thickening and flaking of the epidermis, which is the longest layer of the skin , also showing disorder in the epithelial cells.

A team of researchers from the University Clinic for Dermatology and the Clinical Institute for Laboratory Medicine at MedUni Vienna have now been able to identify new molecular devices as possible causes of suitable starting points for new treatments.

Using patient samples and animal models, the researchers were able to show that a multifactorial protein called “p62” influences the inflammatory changes in infected epidermis and that p62 is inhibited. leading to a reduction of chronic inflammation. Sequestosome 1 / p62 is a multifunctional protein that affects the control of signal movement and cell balance (“homeostasis)” explains Erwin Wagner, head of research from the University Clinic for Dermatology and MedUni ‘s Clinical Institute for Laboratory Medicine Vienna.

The present study therefore examined the role of p62 in the development of atopic dermatitis (AD). Wagner: “For this reason, AD – like skin lesions were induced by a specific genetic inactivation of a gene, called JunB, in keratinocytes – the type of cell found mainly in the epidermis – which to an increase in p62 expression in mouse skin. “The contribution of p62 to pathological changes was then confirmed by additional p62 genetic inactivity.

A new treatment option for AD and related skin diseases

The result: Loss of p62 reduced skin damage, suggesting that inhibition of p62-dependent symptoms may improve the clinical picture of atopic dermatitis (AD) and possibly also associated skin diseases such as psoriasis. The researchers were also able to detect larger amounts of p62 in skin sections from patients with AD and psoriasis. Further studies showed that inactivation of p62 normalized altered differentiation of epidermal keratinocytes, reducing the thickness of the epidermis and reducing the infiltration of immune cells.

“Both visible skin lesions were significantly reduced, as was the circulating immunoglobulin E (IgE) in the blood,” Wagner said, summarizing the results. High levels of IgE are very common in AD patients. At the molecular level, in turn, p62 activates specific signaling pathways that play a key role in inflammatory processes. Without p62 or with therapeutic inhibition, these signaling pathways are not activated, which reinforces the important role of p62 in AD-like inflammation.

These results provide the first in vivo evidence for an inflammatory role of p62 in the skin and suggest that p62-dependent signaling pathways promise therapeutic targets for reducing the skin manifestations of AD and is perhaps also psoriasis. “

Erwin Wagner, Head of Research, Clinic for Dermatology and the Clinical Institute for Laboratory Medicine, University of Vienna Medicine