The study improves understanding of chronic inflammatory skin disease.
Psoriasis is one of the most widespread chronic inflammatory skin conditions, affecting about 250,000 people in Austria. Traditional treatments have largely concentrated on blocking immune cells that drive inflammation. However, new research from MedUni Vienna has demonstrated that it is possible to restore the activity of specific anti-inflammatory immune cells through a targeted approach.
The findings, published in the journal Immunity, mark an important step toward therapies that could act with greater precision while also reducing unwanted side effects.
The Role of Regulatory T Cells
The study, led by Georg Stary (MedUni Vienna’s Department of Dermatology, CeMM), examined the function of regulatory T cells (Treg cells) in chronic inflammatory skin disorders such as psoriasis. These specialized immune cells play a crucial role in keeping the body’s immune response under control and preventing excessive inflammation.
It is already known that these cells lose their regulatory function in chronic skin inflammation, causing the immune response to become uncontrolled and the disease to progress. The researchers have now decoded the exact mechanism behind this for the first time: “We were able to show that the loss of the anti-inflammatory function of regulatory T cells is caused by a malfunction of the cellular metabolism,” says study leader Georg Stary, summarising the research work.
As the researchers’ analyses revealed, the enzyme SSAT plays a key role in the loss of function of Treg cells. SSAT is involved in the regulation of certain molecules (polyamines) that are important for the balance between anti-inflammatory and pro-inflammatory immune cells. If SSAT is produced in increased amounts in Treg cells, they lose their regulatory function and begin to produce pro-inflammatory messenger substances themselves. This fuels the excessive immune response typical of psoriasis.
Targeted interruption of the inflammatory cycle
With the key role of SSAT in the inflammatory process, the researchers have simultaneously discovered a new starting point for therapy: In a mouse model with psoriasis-like skin inflammation, it was shown that inhibiting SSAT can restore the regulatory function of Treg cells and break the cycle of inflammation.
Thus, the development of specific drugs that specifically inhibit SSAT could represent a promising alternative to existing treatment approaches, which are often associated with immunosuppression and increased susceptibility to infection.
“Since other chronic inflammatory diseases of the skin or other organs are also characterised by impaired immune regulation, our approach could be important beyond psoriasis,” says Georg Stary, in the prospect of further studies to advance the development of a treatment option with fewer side effects.
Reference: “The polyamine-regulating enzyme SSAT1 impairs tissue regulatory T cell function in chronic cutaneous inflammation” by Teresa Neuwirth, Daniel Malzl, Katja Knapp, Panagiota Tsokkou, Lisa Kleissl, Anna Gabriel, Baerbel Reininger, Christian Freystätter, Nara Marella, Ana P. Kutschat, Elisabeth Ponweiser, Arvand Haschemi, Davide Seruggia, Jörg Menche, Erwin F. Wagner and Georg Stary, 28 February 2025, Immunity.
DOI: 10.1016/j.immuni.2025.02.011
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