Therapeutic potential of an immunomodulatory enzyme, ScpA, in interferon gamma (IFN-γ) induced skin psoriasis.

Psoriasis is an incurable, immune-mediated inflammatory disease characterized by the hyperproliferation, abnormal differentiation of keratinocytes and a strong interferon gamma inflammatory signature. Interferon gamma plays a crucial role in various cellular processes, including activation of dendritic cells, antigen processing and presentation, cell adhesion and trafficking, and cytokine and chemokine production. These cellular processes are also integral components in the pathogenesis of psoriasis. To gain a deeper understanding of the pathogenesis of interferon gamma -induced psoriasis, psoriatic human epidermis equivalents were developed by stimulating healthy human epidermis equivalents with interferon gamma. Subsequently, the psoriatic human epidermis equivalents were treated with a novel enzyme, Streptococcal C5a peptidase, and compared to treatment using an established psoriasis drug, retinoic acid. Histological evaluation and barrier function assays, including lucifer yellow and biotin penetration assays, revealed that the integrity of the cellular barrier was compromised in samples treated with Interferon gamma alone, whereas treatment with Streptococcal C5a peptidase and retinoic acid successfully restored barrier function. Consistently, immunofluorescence and gene expression analysis of accepted biomarkers of psoriatic pathogenesis indicated that treatment with both drugs markedly reduced the psoriatic human epidermis equivalents phenotype, with greater efficacy observed for Streptococcal C5a peptidase. Thus, Streptococcal C5a peptidase demonstrated a robust modulating ability in restoring skin health in interferon gamma -induced skin psoriasis.