Vitamin D and skin disorders: bridging molecular insights to clinical innovations

Growing evidence demonstrates that the immunoregulatory properties of vitamin D are primarily mediated by its active hormonal form, 1,25-dihydroxyvitamin D3 (calcitriol). This secosteroid modulates immune homeostasis through three principal mechanisms: (1) strengthening antimicrobial defense via innate immune potentiation, (2) downregulating pathological inflammatory cascades, and (3) fine-tuning adaptive immunity through lymphocyte differentiation control. Clinically, serum concentrations of the inactive precursor, 25-hydroxyvitamin D3 (25(OH)D3), exhibit an inverse correlation with systemic immune activation and the prevalence/severity of dermatological conditions, including atopic dermatitis, psoriasis, and systemic sclerosis. Suboptimal 25(OH)D3 levels are thus recognized as a modifiable risk factor for such disorders, with vitamin D3 supplementation demonstrating therapeutic potential in improving clinical outcomes. Furthermore, prolonged vitamin D3 supplementation may reduce disease incidence across a spectrum of dermatopathologies. This review synthesizes contemporary mechanistic and clinical insights into vitamin D's immunoregulatory role in cutaneous diseases. To optimize therapeutic efficacy, future clinical trials should incorporate analysis of vitamin D receptor (VDR) polymorphisms as a predictive biomarker in vitamin D3 intervention strategies.