The outermost skin layer’s epidermis protects the body from external harm. Its renewal depends on stem cells in the deepest layer, which produce new keratinocytes that move upward, differentiating and accumulating proteins as they go. These cells undergo programmed death at the surface, forming a protective layer of dead cells. While the epidermal renewal process is well understood, the specific mechanisms driving it still need to be fully discovered.
A team from the University of Geneva (UNIGE) has discovered condensates in keratinocytes, the epidermis’s skin cells, for the first time. They found that IL-38, a protein, is more concentrated in these aggregates near the skin’s surface, where it is exposed to atmospheric oxygen.
This process may be related to the initiation of programmed cell death in keratinocytes, a key step in epidermal renewal. This finding could offer new insights into studying human skin and skin-related diseases.
Interleukin 38 (IL-38) is a small messenger protein that helps regulate communication between cells. It is primarily known for its role in controlling inflammatory responses. In keratinocytes, the epidermis cells, IL-38 has been linked to maintaining the skin’s immune balance and protecting against excessive inflammation.
Epidermal hemoglobin discovery reveals skin’s protective secrets
Gaby Palmer-Lourenço, associate professor at the Faculty of Medicine of UNIGE and principal investigator of the study, said, “In keratinocytes in vivo, we found that IL-38 forms condensate, specialized protein aggregates with specific biochemical functions, a behavior that was not known for this protein. Even more curious, the closer the keratinocytes were to the skin’s surface, the greater the amount of IL-38 within these condensates.”
Blood vessels are located beneath the epidermis, so oxygen levels decrease as you move from the basal to the top layers of the skin. While oxygen is essential for cell function, it can also lead to oxidative stress, producing free radicals that can harm cells.
The researchers demonstrated that oxidative stress triggers the condensation of IL-38 in keratinocytes under laboratory conditions, suggesting a link between oxidative stress and IL-38’s role in the skin’s response to environmental factors.
Gaby Palmer-Lourenco said, “Our results lead us to believe that, as we move closer to the epidermal surface, the increasing oxygen concentration promotes the formation of protein condensates, indicating to keratinocytes that they are in the right place to enter cell death.”
Can stress really turn your hair grey?
This hypothesis offers new insights into the mechanisms of epidermal renewal and may help better understand the pathological processes behind skin diseases like psoriasis and atopic dermatitis. The research group plans to explore these questions further in future studies.
Alejandro Díaz-Barreiro is already working on the next step: “In the model we used previously, the effects of oxidative stress were artificially induced in a single layer of keratinocytes, a scenario that differs from the actual situation in the skin.”
“We are developing a new experimental system to apply oxygen gradients to in vitro reconstituted human epidermis. In this model, only the skin surface will be exposed to ambient air, while the other layers will be protected. This will allow us to study the effect of oxidative stress on epidermal renewal in detail.”
“By enabling a more precise analysis of human cells, this new system will provide an alternative to animal models often used for studying skin biology and disease.”
Journal Reference:
- Alejandro Diaz-Barreiro, Gea Cereghetti et al. Oxidation-sensitive cysteines drive IL-38 amyloid formation. Cell Reports. DOI: 10.1016/j.celrep.2024.114940