Psoriasis is a chronic autoimmune disease that causes red, scaly plaques on the skin, which are often accompanied by intense itching, burning, and dryness.

It affects 2.4% of the population, which represents more than 1,100,000 patients diagnosed in Spain.

It originates when the immune system becomes excessively activated (stress can trigger outbreaks) and produces substances that irritate the skin.

A research team from the Severo Ochoa Molecular Biology Center of the Higher Council for Scientific Research and the Autonomous University of Madrid (CBM-CSIC-UAM) has discovered a until now unknown mechanism that promotes inflammation processes in diseases such as psoriasis.

The work, published in the journal “Journal of Allergy and Clinical Immunology”, also shows that A drug already approved to treat certain types of leukemia (dasatinib) blocks a specific pathway of the immune system and reduces inflammation associated with psoriasis in an experimental model of this disease.

Dasatinib acts as a switch that stops that process, which involves different molecules that immune cells use to communicate with each other.

Among these molecules, cytokines stand out, small proteins that act as chemical signals. One of these signals, called interleukin 23 (IL-23), activates certain immune cells and prompts them to produce another inflammatory molecule called IL-17, which helps trigger inflammation in the skin.

This “dialogue” between the two interleukins (IL-23 and IL-17) is one of the main drivers of psoriasis, and when the inflammation is stopped, it decreases.

Although in recent years treatments have been developed that block these signals and have greatly improved the control of the disease, little is still known about how the interleukin 23 signal is transmitted within cells, something very important for finding new therapeutic targets. And this study focuses precisely on that internal mechanism.

Drug repositioning

To study this process, the researchers used immune system cells capable of responding to the IL-23 signal. To do this, they evaluated drugs that are already approved for other diseases in order to identify new therapeutic uses, a strategy called drug repositioning. This approach allows us to study compounds whose safety and basic functioning are already known, which facilitates faster progress towards clinical applications in new contexts.

In this case, the team analyzed a collection of drugs authorized by regulatory agencies and observed that some of them interfered with the inflammatory pathway activated by the IL-23 molecule. And among all of them, dasatinib, currently used in certain types of leukemia, stood out for its ability to block the production of IL-17 in immune system cells.

Experiments showed that dasatinib effectively blocks IL-23-induced IL-17 production in immune cells. That is, dasatinib acts as a switch that turns off the inflammatory signal.

They then tested whether this inhibitory effect could also be observed in an experimental model of psoriasis-like skin inflammation. And the results showed that treatment with dasatinib reduced several characteristic signs of this disease, such as thickening of the skin, the accumulation of immune cells in the inflamed area and the presence of IL-17-producing cells.

These effects were observed when the drug was administered systemically (it reaches the entire body through the blood), and also when it was applied directly to the skin, which suggests the possibility of being able to apply it locally in the form of creams, avoiding exposure of the rest of the body to the drug.

The study also made it possible to identify how the inflammatory signal is transmitted within cells. They discovered that IL-23 activates a chain of proteins that function as molecular switches and end up activating cellular complexes called mTOR, which regulate the activity and metabolism of cells, and are important in the inflammation process.

A specific protein called Blk participates in this process, which acts as an intermediary between the IL-23 signal and the activation of the inflammatory response. Until now, it was not known that Blk acted as a mediator in the inflammatory cascade of psoriasis, so this finding opens a new therapeutic target for future treatments.

Taken together, the results of this research describe a new molecular pathway that helps explain how inflammatory responses associated with psoriasis are activated. Furthermore, they suggest that existing drugs such as dasatinib could be explored in the future as possible treatments for inflammatory diseases related to this pathway.

Although more studies will be necessary to evaluate its safety and effectiveness in this context, the work opens new avenues for the development of therapies against chronic inflammatory diseases.