The role of another potential culprit in the cellular and genetic pathways that contributes to the formation of psoriasis lesions is unmasked by the findings at Fujita Health University, Japan, published in the journal Scientific Reports.
Psoriasis Vulgaris is a chronic autoimmune condition characterized by skin inflammation, scales, and dry patches, affecting more than 130 million people around the world. The body's immune cells - T-cells, macrophages, and dendritic cells start attacking the healthy skin tissue, that triggers the inflammatory process and proliferation of skin cells, leading to red, painful plaque-like lesions experienced by these patients.
Novel Immune Pathway of Psoriasis:
The cells have pro-inflammatory effects as they burst open and release their contents at the site of infection, thereby forming "neutrophil extracellular traps" (NETs) - a web of proteins and genetic information from its nucleus and induce inflammation.
The activation of NETs in psoriasis is performed by a precursor signaling protein called IL-36 cytokines. The mutation in the Il36rn gene causes a deficiency of the IL-36 receptor antagonist (IL-36Ra) protein, thereby allowing the IL-36 to induce uncontrolled inflammation.
This results in the proliferation of epidermal cells and increased neutrophil count in psoriasis-like lesions in the mutant mice, in a condition known as DITRA.
The observation was proven by using imiquimod, a drug known to stimulate IL-36 signaling and subsequent immunological response, to induce psoriasis in two groups of mice: one healthy (wild type) and another with the Il36rn gene mutation.
The mutant mice also had higher neutrophil counts and NET concentrations than the wild type, and thus mRNA levels of target cytokines were also examined.
Use of a drug that specifically targets and inhibits PAD4an enzyme responsible for the formation of NETs - Cl-amidine, significantly reduced the levels of inflammatory cells and IL-36 signalling proteins. This resulted in a decrease of psoriasis lesions just after three days of treatment.
"By providing mechanistic insights into the involvement of neutrophils in psoriasis pathogenesis, our study provides new directions for developing novel promising therapeutic approaches, potentially revolutionizing the quality of life of thousands of people suffering from particularly severe forms of psoriasis", says Dr. Soichiro Watanabe, Fujita Health University.