Extracellular matrix remodeling as an immune-regulatory mechanism in psoriasis: Implications for tissue persistence and relapse.

Although cytokine-targeted therapies have transformed psoriasis management, persistent tissue abnormalities and relapse after clinical remission indicate that immune suppression alone does not fully restore tissue homeostasis. This critical narrative review evaluates whether extracellular matrix (ECM) remodeling is merely a consequence of inflammation or can help maintain a relapse-permissive tissue state. In lesional skin, basement membrane disruption, disorganized dermal matrix architecture, altered collagen deposition, hyaluronic acid metabolism and proteoglycan expression, together with increased matrix metalloproteinase activity, especially matrix metalloproteinase-2 (MMP-2) and MMP-9, reshape the microenvironment in which keratinocytes, stromal cells, endothelial cells and immune cells interact. Mechanistic studies indicate that these abnormalities can affect dermal-epidermal integrity, leukocyte trafficking, angiogenesis, vascular permeability and matrix-derived inflammatory signaling. Collagen crosslinking and dermal stiffening add a mechanical layer to psoriatic inflammation through mechanotransductive pathways. ECM-derived biomarkers and imaging approaches remain promising research tools for assessing tissue remodeling, but they have not yet been validated as psoriasis-specific clinical biomarkers. ECM-targeted interventions may complement cytokine-directed therapy, although most remain at the preclinical or early translational stage. Overall, ECM remodeling provides a complementary framework for understanding psoriasis as a disease involving both immune activation and persistent tissue-level remodeling.