Scientists in Belgium have discovered a key mechanism that protects the skin from inflammation, opening the door to new treatments for chronic skin diseases. The study highlights the role of the protein ATG9A in preventing inflammatory disorders.
A team of researchers at Vlaams Instituut voor Biotechnologie (VIB) and Ghent University has made a remarkable breakthrough in understanding and potentially managing skin inflammation. Their findings, published in the journal Immunity, shed light on the mechanisms that could pave the way for innovative treatments for chronic skin conditions, such as psoriasis and lupus.
The research centered on ATG9A, a protein instrumental in a cellular cleanup process known as autophagy. This process ensures that skin cells remain healthy by removing harmful proteins before they accumulate and trigger inflammation.
The team from the VIB-UGent Center for Inflammation Research (IRC) utilized advanced mouse models and patient data to demonstrate that a lack of ATG9A leads to severe skin disease due to a cascade of inflammatory signals.
“ATG9A seems to act as a master repressor of skin inflammation,” first author Dario Priem, an IRC postdoctoral researcher, said in a news release. “By directing inflammatory proteins toward autophagy, ATG9A is capable of shutting down multiple inflammatory pathways.”
The researchers uncovered a significant link between tumor necrosis factor (TNF) and type I interferons (IFNs), two molecules known to drive skin disease such as psoriasis. They found that in the absence of ATG9A, TNF triggers an abnormal IFN response via a molecule called ZBP1, leading to massive cell death and subsequent skin damage.
Current treatments for skin diseases such as psoriasis often rely on anti-TNF therapies, which can result in severe side effects.
The identification of the TNF–IFN–ZBP1 pathway offers potential for developing more targeted and safer treatments. This pathway could also have broader applications, such as managing other TNF-driven inflammatory diseases like rheumatoid arthritis and inflammatory bowel disease.
“This discovery not only deepens our understanding of how the immune system is regulated, m but it also highlights promising new drug targets for patients suffering from skin disease or other chronic inflammatory pathologies,” added senior author Mathieu JM Bertrand, an associate professor at the University of Ghent and IRC research leader.