The role of matrix metalloproteinase 9 in immune-mediated skin diseases

MMP-9, dependent on zinc, is a key endopeptidase involved in tissue homeostasis, inflammation, and immune-related pathological processes through its role in extracellular matrix degradation and remodeling. Compared with other immune-associated skin diseases, compelling evidence indicates aberrant MMP-9 expression in psoriasis, vitiligo, bullous pemphigoid, and melanoma. MMP-9 modulates the pathological progression of these disorders through multiple mechanisms, including regulation of immune responses, inflammatory cascades, angiogenesis, and tissue remodeling, thereby demonstrating considerable translational potential. MMP-9 emerges as a promising biomarker and therapeutic target, but clinical validation remains limited. Currently, the clinical application of MMP-9 inhibitors is plagued by several critical drawbacks, such as poor selectivity, off-target effects, severe toxic side effects, and unsatisfactory therapeutic efficacy. Therefore, the exploration of novel MMP-9 inhibitors and the conduction of well-designed, adequately powered clinical trials are urgently warranted and of great clinical necessity. This comprehensive review systematically examines the molecular regulatory network of MMP-9 in immune-mediated dermatological disorders and evaluates its translational capacity as a biomarker and therapeutic target, along with its clinical applications and key challenges.