In the paper, the authors note that most previous treatment approaches for psoriasis have mainly focused on inhibiting pro-inflammatory immune cells. The investigators say their findings may pave the way for developing a therapy that works more precisely and is associated with fewer side effects.
The research team is led by Georg Stary, MD, from the Medical University of Vienna's Department of Dermatology. They focused their investigations on the role of regulatory T cells (Treg cells) in chronic inflammatory skin diseases such as psoriasis. Treg cells specialize in preventing excessive immune responses and, thus, 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 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,” said Dr. Stary in a press release.
As the researchers' analyses revealed, the enzyme SSAT plays a key role in the loss of function of Treg cells. SSAT is involved in regulating 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 production of pro-inflammatory substances fuels the excessive immune response typical of psoriasis.
By better understanding the key role of SSAT in the inflammatory process, the researchers have discovered a new starting point for therapy. In a mouse model with psoriasis-like skin inflammation, the investigators showed that inhibiting SSAT can restore Treg cells' regulatory function and break the inflammation cycle.
This finding suggests the development of medications 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 characterized by impaired immune regulation, our approach could be important beyond psoriasis,” said Dr. Stary.
The authors hope further studies will advance the development of a treatment option with fewer side effects.
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