Vitamin D Modulates Antimicrobial Peptides in Skin, Influencing Innate Immunity and Repair

The skin acts as the body's primary barrier, relying on innate defense factors like antimicrobial peptides (AMPs) for pathogen defense, inflammation regulation, and tissue repair. While Vitamin D is classically known for bone metabolism, experimental and translational studies increasingly show its role in modulating AMP expression and processing. This suggests a critical link between Vitamin D signaling and cutaneous innate immunity, yet the functional consequences of this axis are highly context-dependent, presenting a gap in understanding its full therapeutic potential.

This comprehensive review synthesized existing evidence from diverse research modalities to elucidate the intricate relationship between Vitamin D signaling and cutaneous innate immunity, specifically focusing on its modulation of antimicrobial peptides (AMPs). Researchers analyzed findings from cell-based studies, various animal models, human skin samples, and limited clinical studies. The review aimed to identify the mechanisms by which Vitamin D influences AMPs and to assess the functional implications of this axis in skin health and disease, including antimicrobial defense, inflammatory regulation, angiogenesis, and tissue repair.

Vitamin D modulates the expression and processing of selected antimicrobial peptides (AMPs) through both VDR-dependent and non-classical pathways, linking Vitamin D signaling to cutaneous innate immunity. Evidence from various models suggests this axis contributes to antimicrobial defense, inflammatory regulation, angiogenesis, and tissue repair. However, the functional outcomes of Vitamin D-mediated AMP regulation are highly context-dependent. Despite promising preclinical data, direct clinical evidence demonstrating therapeutic benefit through AMP modulation remains limited and often inconsistent. The review identified significant gaps, including the need to understand context-dependent AMP functions in diverse skin environments and their interactions with the skin microbiota. > The most significant finding is the consistent observation of Vitamin D's mechanistic influence on AMPs, contrasted with the current lack of robust, direct clinical evidence for therapeutic benefit.