Vitamin D is classically recognized as a regulator of calcium and phosphate metabolism. It has also emerged as a crucial immunomodulator. Both innate and adaptive immune cells express the vitamin D receptor and possess the enzymatic machinery necessary to convert vitamin D into its biologically active form. Through genomic and rapid non-genomic actions, vitamin D can modulate antimicrobial peptide expression and cytokine secretion, and regulate epithelial and endothelial barrier integrity, thereby strengthening the first line of defense against external agents. In adaptive immunity, calcitriol promotes a shift toward a more tolerogenic phenotype by suppressing Th1/Th17 and B cell activity while pro- moting Th2 and regulatory T cell responses, thereby reducing the production of autoantibodies and ultimately limiting autoimmune responses. Epidemiological studies consistently associate vitamin D deficiency with increased suscepti- bility to infections, including respiratory tract diseases and sepsis, as well as autoimmune disorders such as multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus. Although clinical trial results remain heterogeneous, maintaining 25(OH)D3 serum levels above 30–50 ng/mL is essential for sustaining optimal immune system function. Giv- en the high global prevalence of vitamin D insufficiency, strategies such as safe sun exposure, dietary fortification, and supplementation represent cost-effective interventions. Further mechanistic and clinical research is needed to elucidate the molecular basis of the immunomodulatory properties of vitamin D and to define optimal dosing and therapeutic ap- plications in immune-related disorders.
