Programmed cell death of keratinocytes: an active driver in psoriasis

Psoriasis is a common, chronic inflammatory skin disorder with a high prevalence across all age groups, imposing a substantial burden on both individuals and society. It is characterized by epidermal hyperplasia and infiltration of immune cells into the dermis. Within the psoriatic microenvironment, epidermal keratinocytes contribute to a self-amplifying inflammatory response through the generation of "feed-forward" inflammation. Contrary to the earlier view of keratinocytes as passive "victims" in psoriasis pathogenesis, growing evidence supports their role as "active drivers" of disease progression. Programmed cell death (PCD) in keratinocytes interacts dynamically with immune cells, cytokines, damage-associated molecular patterns (DAMPs), and other factors, forming a complex regulatory network. Multiple PCD-related molecules in keratinocytes have been identified, many of which hold promise as biomarkers or therapeutic targets. These molecules may inform the development of new diagnostic and treatment strategies for psoriasis. This review outlines the major PCD pathways in keratinocytes-apoptosis, necroptosis, ferroptosis, and pyroptosis-and examines their roles in psoriasis. We also summarize recent therapeutic advances that modulate keratinocyte cell death and discuss how these pathways shape the cutaneous immune microenvironment.