Skin barrier dysfunction and correlation with the onset and progression of psoriasis

The skin barrier serves as the body's primary line of defense against exogenous insults and is critical for maintaining systemic homeostasis. Emerging evidence indicates that skin barrier dysfunction is not merely a secondary manifestation of psoriasis, but rather an early and pivotal pathogenic driver of the disease. It exerts bidirectional crosstalk with immune dysregulation, genetic predisposition and environmental triggers, collectively contributing to the initiation and progression of psoriasis. This review first elaborates on the normal structural composition and physiological functions of the skin barrier, followed by a discussion of the major etiological factors of psoriasis and the underlying mechanisms by which barrier impairment promotes psoriasis pathogenesis. These mechanisms include aberrant keratinocyte hyperproliferation, abnormal expression of structural proteins, tight junction disruption, aquaporin 3 dysfunction and dysregulated cutaneous lipid metabolism. Furthermore, we highlight the clinical significance of skin barrier restoration in psoriasis management and propose directions for future research. Elucidating the intricate crosstalk between skin barrier dysfunction and psoriasis pathogenesis will facilitate the identification of novel diagnostic biomarkers and the development of targeted therapeutic strategies for this disease.