Modulation of the immune system by UV radiation: more than just the effects of vitamin D?

Key Points Ultraviolet (UV) irradiation of skin and consequent suppression of local and systemic immune responses have been associated with reduced severity of some inflammatory and immune diseases. Vitamin D deficiency has been linked with immune diseases such as multiple sclerosis and allergic asthma. The suppression of immune responses and the induction of antimicrobial peptides by vitamin D may contribute to these associations. Humans obtain most of their vitamin D by exposure of skin to sunlight. The benefits of moderate UV radiation exposure (and positive latitude gradients for diseases) may reflect UV-induced vitamin D production. UV irradiation of skin can affect the manifestation of local diseases (for example, psoriasis) and cause altered responses to topical or intradermal antigens. Vitamin D is a candidate mediator for these effects. However, for the suppression of systemic diseases (such as multiple sclerosis and asthma), the links between UV radiation and UV-induced vitamin D are more equivocal. In multiple sclerosis, further evidence is needed to determine whether the positive latitude gradient for disease prevalence is influenced by UV radiation independently of vitamin D. For allergic asthma, a positive latitude gradient has been recently reported and vitamin D intervention studies have been promising. It is likely that UV irradiation of skin affects human immune outcomes by multiple modulatory pathways, and different stages of disease pathogenesis may vary in their response to UV-induced regulatory molecules and vitamin D. By inducing antimicrobial peptides and exerting immunosuppressive effects, UV radiation and vitamin D may provide an adjunctive therapy for some diseases through microbial control with reduced tissue damage. In addition, vitamin D may modulate the development of innate immune responses through effects on gut flora. Other UV-induced mediators (namely, cis -urocanic acid and oxidation products of DNA, lipids and proteins) may contribute to the consequent systemic immunomodulation following UV irradiation. Ultraviolet radiation from sunlight can modulate immune function by both vitamin D-dependent and -independent mechanisms. The authors discuss the implications of this for understanding whether vitamin D supplementation might benefit patients with autoimmune diseases and allergic asthma, and boost immunity to pathogens. Humans obtain most of their vitamin D through the exposure of skin to sunlight. The immunoregulatory pr