A research team led by Erwin F. Wagner from the Medical University of Vienna has discovered a previously unknown molecular mechanism that contributes to the development of psoriasis – and at the same time represents a potential biomarker for a new treatment concept. The study published in Cell Death & Differentiation shows that a specific fatty acid-binding protein (FABP5) drives ferroptosis, a certain form of cell death, and amplifies inflammatory processes in the skin. Blocking this protein significantly improved the skin changes typically associated with psoriasis.

Until now, the chronic inflammatory skin disease psoriasis has been associated with overactivity of the immune system. Now, the scientific team led by Erwin Wagner (Department of Dermatology and Department of Laboratory Medicine, MedUni Vienna) and Kazuhiko Matsuoka (Center for Cancer Research, MedUni Vienna) with first author Kamil Mieczkowski (Department of Laboratory Medicine) has shown for the first time that changes in the fat metabolism of skin cells also contribute significantly to the development and progression of inflammation.

Scientific analyses show that skin samples from psoriasis patients and a corresponding animal model contain significantly elevated levels of the fatty acid-binding protein FABP5, while a certain protective enzyme (GPX4) is detectable at reduced levels. According to the researchers, this imbalance triggers an inflammatory cascade through ferroptosis that is typical of the clinical picture of psoriasis. At the same time, the team found that skin inflammation can be significantly reduced by pharmacological blockade of FABP5 and ferroptosis.

Possible addition to immunomodulatory therapies
"Our results show that psoriasis is caused not only by a misdirected immune response, but also by changes in the fat metabolism of skin cells," says Erwin Wagner. "FABP5 could therefore serve as a biomarker in the future for developing new, targeted therapies," Kazuhiko Matsuoka adds. This could be of particular benefit to patients who do not respond well to existing immunomodulatory approaches such as biologics.

The researchers also emphasise that FABP5 could be important not only for psoriasis, but also for other inflammatory diseases such as atopic dermatitis. Since psoriasis is often associated with metabolic and cardiovascular diseases, the study results also provide clues to possible common causes of these diseases. Further studies are needed to deepen and confirm the newly gained insights into the relationship between fat metabolism and inflammatory processes.