A review of core immuno-inflammatory mechanisms and key regulatory targets in psoriasis

Psoriasis is a chronic immune-mediated inflammatory skin disease caused by dysregulated interaction between innate and adaptive immune cells. Of note, the IL-23/Th17 axiom is new central circuit amongst known pathways, while TNF-alpha, IL-17 family cytokines and IL-36 mediate the dysfunction of keratinocyte and tissue in inflammation. An interconnecting inflammatory network involves dendritic cells, T-cell populations, keratinocytes, neutrophils and fibroblasts that plate epidermal hyperproliferation and lesional immune-cell recruitment. Biologics targeting TNF-alpha and IL-17 and IL-23 are clinically transformative in the treatment of disease, but a large cohort of patients are left with incomplete response, resistance or challenges in long-term management. Other novel targets such IL-36R and AHR may extend the window of therapeutic opportunity. Molecular stratification and biomarker-driven treatment selection also merit investigation in parallel with further delineation of a specific therapeutic strategy.