University of Geneva Researchers Explore Epidermal Regeneration and Its Link to Skin Diseases. A team of researchers from the University of Geneva (UNIGE) made a discovery about interleukin-38 (IL-38), a protein involved in regulating inflammation, and its unexpected role in the natural skin renewal process of human skin.
Published in the journal Cell Reports, the study sheds new light on the mechanisms behind epidermal regeneration. It suggests potential pathways for understanding and treating skin conditions like psoriasis and atopic dermatitis.
The Complex Process of Epidermal Skin Renewal
The epidermis, the outermost layer of skin, is a vital protective barrier against environmental stressors. It is a specialized skin cells that migrate to the surface. As these keratinocytes move upward, they differentiate, accumulate protein aggregates, and ultimately undergo cell death (cornification). This forms a layer of dead cells that shield the body.
While the basic steps of this renewal process are well-documented, many underlying mechanisms remain unclear. “How the epidermis constantly renews itself is well documented. However, the mechanisms that drive this process are still not fully understood. According to Gaby Palmer-Lourenço, associate professor at the UNIGE Faculty of Medicine and the study’s lead investigator.
IL-38 and Protein Condensates: A Surprising Discovery in Skin Renewal
Interleukin-38 is a protein previously known for regulating inflammatory responses and maintaining the skin’s immune balance. However, this study revealed a previously unknown behavior of IL-38 in keratinocytes: it forms specialized protein aggregates, or condensates, with specific biochemical functions.
The researchers found that the closer keratinocytes are to the surface of the epidermis—where oxygen levels are higher—the more IL-38 condensates they produce. “We were able to show that oxidative stress does indeed cause IL-38 condensation under laboratory conditions,” explained Alejandro Díaz-Barreiro, a postdoctoral fellow at UNIGE and the study’s first author.
Implications for Skin Disease Research
This discovery provides insights into epidermal renewal and offers potential pathways better to understand skin diseases such as psoriasis and atopic dermatitis. These conditions often involve disruptions in keratinocyte behavior and immune responses, and the role of IL-38 in these processes could hold critical answers.
To build on these findings, the research team is developing a new experimental system that mimics the real-world oxygen gradients of human skin. Unlike previous models, this system will expose only the surface of the reconstituted human epidermis to ambient air while protecting the lower layers. “This will allow us to study in detail the effect of oxidative stress on epidermal renewal,” Díaz-Barreiro explained.
A Step Toward Better Treatments
This system could provide an alternative to animal models often used in skin biology research by enabling a more precise analysis of human skin cells. The team hopes their work will contribute to the development of better treatments for skin conditions by targeting the pathological mechanisms underlying these diseases.
The study marks an important step toward unraveling the complexities of skin renewal and opens new doors for research into improving skin health and treating chronic conditions. With further exploration of IL-38 and its role in keratinocyte behavior, researchers may soon unlock new ways to tackle stubborn skin diseases.
Reference: Alejandro Diaz-Barreiro, Gea Cereghetti, Francisco Gabriel Ortega Sánchez, Jenna Tonacini, Dominique Talabot-Ayer, Sylvie Kieffer-Jaquinod, Vera Maria Kissling, Arnaud Huard, Christopher Swale, Tuomas P.J. Knowles, Yohann Couté, Matthias Peter, Antonio Francés-Monerris, Gaby Palmer. Oxidation-sensitive cysteines drive IL-38 amyloid formation. Cell Reports, 2024
