Vitamin D and antimicrobial peptides in skin health and disease: Mechanisms and therapeutic potential

As the body's frontline barrier against the external environment, the skin maintains homeostasis through a complex network of innate defense factors, among which antimicrobial peptides (AMPs) play pivotal roles in pathogen defense, inflammation regulation, and tissue repair. Apart from its classical role in bone metabolism, Vitamin D has been shown, mainly in experimental and translational studies, to modulate the expression and processing of selected AMPs through VDR-dependent and non-classical pathways. These findings suggest a possible link between Vitamin D signaling and cutaneous innate immunity. However, the functional consequences of Vitamin D-mediated AMP regulation appear to be highly context-dependent. Evidence from cell-based studies, animal models, human skin samples, and limited clinical studies suggests that this axis may participate in antimicrobial defense, inflammatory regulation, angiogenesis, and tissue repair, but direct clinical evidence demonstrating therapeutic benefit through AMP modulation remains limited and sometimes inconsistent. Finally, building on current evidence, we analyze the limitations of research on the Vitamin D-AMP axis and highlight future directions, including the context-dependent functions of AMPs in diverse skin environments, their interactions with the skin microbiota, and the design and evaluation of translational studies. We argue that this review not only advances our understanding of skin immune mechanisms but also provides valuable insights and references for future research.