Blocking the c-Jun activating protein may help treat psoriasis symptoms.

The "c-Jun" protein may play a major role in the development of psoriasis, but inhibiting this protein may alleviate symptoms, new research suggests.

c-Jun belongs to a larger family of transcription factors, DNA-binding factors, known as Activator Protein-1 (AP-1). Previous studies have identified a significant role of these AP-1 proteins in psoriasis in dermal epithelial cells but its function in immune cells was not yet clear. 

"In order to answer this question, we examined whether AP-1 proteins in immune cells have a role in the pathogenesis of psoriasis. We identified elevated values of c-Jun in dendritic cells in skin sections of psoriasis patients," says study author Philipp Novoszel from MedUni Vienna's Institute of Cancer Research, in a news release. "To further investigate the role of c-Jun, we deactivated the gene specifically in dendritic cells." 

When psoriasis-like skin inflammation was triggered, the deactivation of c-Jun reduced epidermal thickening and decreased the infiltration of immune cells, he says.

Pharmacological inhibition of the c-Jun activating protein, known as JNK (c-Jun N-terminal Kinase), was effective. "That represents a potential treatment option, since highly effective, selective JNK inhibitors are available and could be investigated," stresses Novoszel. 

A further analysis using human dendritic cells showed that c-Jun controls the secretion of a key molecule in the development of psoriasis, cytokine interleukin-23 (IL-23). High values are characteristically found in psoriasis patients and lead to activation of disease-triggering T cells. "The inhibition of c-Jun-dependent signal transmission could improve the clinical picture of psoriasis by reducing pathogenic IL-23."

The research appears in Embo Molecular Medicine.