Taneesa Williamson Is this the key to treating chronic inflammatory skin conditions?
Recent research from the University of California San Diego School of Medicine has shed light on a remarkable protein, ZNF750, and its essential role in maintaining skin health. This study, published in the journal ‘Immunity’, reveals that ZNF750 not only strengthens the skin barrier but also actively reduces skin inflammation. These findings offer new hope for addressing chronic skin conditions such as psoriasis and seborrheic dermatitis.
The role of ZNF750 in skin cells
ZNF750 is primarily found in keratinocytes, the main cells that make up the outermost layer of the skin, known as the epidermis. As keratinocytes grow and mature, they form the skin barrier that protects us from environmental aggressors such as pathogens, allergens, and toxins.
However, the study reveals that ZNF750 does more than help form the skin barrier. It plays a critical role in managing the skin’s immune response by working closely with another molecule, KDM1A/LSD1, a histone demethylase. Together, these molecules suppress genes that encode pattern recognition receptors (PRRs).
PRRs, such as TLR3, IFIH1/MDA5, and DDX58/RIG1, act as the skin’s sensors for detecting threats like infections or tissue damage. When activated, these receptors signal the body to launch an immune response, which often includes inflammation. While this process is crucial for healing and protecting the skin, it can also lead to problems if left unchecked. Overactive PRRs are associated with inflammatory skin conditions that cause discomfort and long-term damage.
How ZNF750 controls inflammation
The research team discovered that as keratinocytes mature and move closer to the skin’s surface, ZNF750 and KDM1A reduce the activity of PRRs. This suppression helps to prevent unnecessary inflammatory responses, ensuring that the skin does not remain in a constant state of alert.
This process is particularly significant given the skin’s constant exposure to potential irritants, such as pollution, ultraviolet (UV) radiation, and pathogens. Without ZNF750’s regulatory function, the skin would likely experience ongoing inflammation, leading to chronic conditions.
In their experiments, the researchers found that a deficiency in ZNF750 or KDM1A caused keratinocytes to retain higher levels of PRR activity. This deficiency resulted in an exaggerated immune response, suggesting that ZNF750 is crucial for maintaining a healthy balance between immune defense and inflammation.
Implications for skin health and treatments
One of the most striking aspects of this discovery is how it deepens our understanding of why some people are more prone to chronic inflammatory skin disorders. Conditions like psoriasis, characterised by red, scaly patches, and seborrheic dermatitis, which causes itchy, flaky skin, may stem from an imbalance in the ZNF750 and KDM1A system. When these molecules are not functioning properly, PRRs remain overly active, fueling persistent inflammation.
The study’s authors highlighted this connection, noting, “Our findings explain how the skin’s surface prevents excessive inflammation through ZNF750- and KDM1A-mediated suppression of PRRs.” This insight not only clarifies the biological mechanisms behind skin health but also opens the door for new treatments.
Looking ahead: Potential therapies
The identification of ZNF750’s role in controlling skin inflammation could pave the way for innovative therapies aimed at boosting its function. By enhancing ZNF750 or mimicking its effects, researchers may be able to develop targeted treatments for inflammatory skin disorders. Such treatments would focus on reducing excessive PRR activity without compromising the skin’s natural defence mechanisms.
This discovery could have implications beyond dermatology. Understanding how ZNF750 regulates inflammation may inspire similar research in other tissues and organs where inflammation plays a key role in disease.
Read our latest issue below:
There are 5 ways you can catch up with SPA+CLINIC
- Our quarterly print magazine, delivered to your door. Subscribe here.
- Our website, which is updated daily with its own completely unique content and breaking news.
- Our weekly newsletter – free to your inbox! Subscribe here.
- Our digital magazine – click here to view previous issues.
- Our social media – see daily updates on our Instagram, Facebook & Linkedin
