New breakthrough in psoriasis research: inflammation stopped by fatty acids!

New breakthrough in psoriasis research: inflammation stopped by fatty acids!

A research team from Mainz University Medical Center has discovered a novel metabolic mechanism in immune cells that provides important insights into the autoimmune disease psoriasis. In a current study, scientists led by Univ.-Prof. Dr. Tim Sparwasser examined the role of gamma delta T17 cells, a special type of T cell that is involved in the inflammatory response in psoriasis. These cells produce the pro-inflammatory cytokine interleukin-17A (IL-17A), which plays a central role in the inflammatory processes of this skin disease. The research team identified fatty acid production as an essential metabolic process that drives the inflammatory response.

The results, published in the specialist journalNature Metabolism, show that gamma-delta T17 cells undergo a metabolic reprogramming process during psoriatic inflammation. What is particularly noteworthy is that blockade of acetyl-CoA carboxylase 1 (ACC1) can significantly reduce IL-17A production and inflammation. This opens up new opportunities for the development of drugs to treat psoriasis and potentially other inflammatory diseases.

Relevance of psoriasis

Psoriasis is a chronic inflammatory skin disease that is one of the most common skin diseases worldwide. In Germany, around 2% of the population is affected. The symptoms are clear and painful: red, scaly skin coupled with itching and burning significantly affect the quality of life of those affected. In addition, the condition results in several health risks, including increased cardiovascular risk and the possibility of psoriatic arthritis.

What is particularly alarming is that up to 30% of psoriasis patients develop psoriatic arthritis within ten years, often leading to delays in diagnosis that can lead to permanent joint damage. Proinflammatory cytokines such as TNF-α, IL-17 and IL-23 play a crucial role here. These cytokines are produced by activated T helper cells and dendritic cells and lead to hyperproliferation of keratinocytes. A central mechanism in immunopathogenesis is the IL-23/IL-17 axis, which is responsible for the progression and maintenance of psoriasis.

A new therapeutic approach

The newly discovered connection between gamma-delta T17 cell metabolism and fatty acid production could promote the development of specific therapies. The challenge, however, lies in specifically blocking fatty acid synthesis in T cells in order to reduce the pro-inflammatory properties of these cells. The findings regarding the role of the regulator PRDM16 in the differentiation of gamma delta T17 cells expand the understanding of the immune response and its metabolic regulation. Studies show that PRDM16 plays a negative role in the differentiation of γδT17 cells, suggesting the importance of lipids in the function of these cells.

Another challenge is the analysis and transfer of these findings into clinical practice. Biologics that target IL-17A or IL-23 blockade are already showing promising results in the treatment of moderate to severe psoriasis, achieving significant skin improvements in approximately 90% of patients. Future research could use these newly identified mechanisms to further refine therapeutic approaches and potentially apply them to related autoimmune diseases such as rheumatoid arthritis and inflammatory bowel disease.