The role of antimicrobial peptides in rheumatoid arthritis: From mucosal predisposition to chronic synovitis

Antimicrobial peptides (AMPs) play many roles in immune regulation, integrating direct antimicrobial activity with potent immunomodulatory functions to coordinate host defence. However, these same signals can become maladaptive and contribute to the development and persistence of chronic inflammatory diseases such as rheumatoid arthritis (RA). In the inflamed joint, AMPs can disrupt tissue architecture, activate resident and infiltrating immune cells through multiple mechanisms, such as neutrophil extracellular trap formation, and may themselves serve as autoantigens, thereby amplifying pathogenic immune responses. Conversely, the pleiotropic nature of AMPs also presents opportunities for their exploitation as biomarkers of disease activity or as direct therapeutic agents to treat RA. This review examines the contributions of human AMPs to RA pathogenesis, with a particular focus on their actions within the synovial microenvironment, including both fibroblast populations and infiltrating immune cells during chronic inflammation.