Role of Antimicrobial Peptides in the Pathogenesis of Atopic Dermatitis

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by barrier dysfunction, immune dysregulation, and microbial dysbiosis. Recent studies have highlighted the multifaceted roles of antimicrobial peptides (AMPs) both as innate defenders against microbial invasion and as regulators of immune responses and skin barrier homeostasis. This review synthesizes the current knowledge on the dysregulation of AMP expression in AD, the impact of Th2-dominant inflammation on AMP-mediated defense, and the complex relationship between AMP activity and the cutaneous microbiota (particularly in the context of Staphylococcus aureus colonization). We also explore the immunomodulatory and barrier-stabilizing functions of AMPs, emphasizing their dual roles as both protective and potentially pathogenic agents depending on their expression levels and processing. Furthermore, emerging therapeutic strategies that aim to restore AMP function (such as vitamin D signaling, aryl hydrocarbon receptor activation, and synthetic AMPs) are discussed. A deeper understanding of AMP-related mechanisms in AD may offer novel insights for precision-targeted interventions that simultaneously address inflammation, barrier repair, and microbial imbalance.