The controversial role of vitamin D in the skin: immunosuppression vs. photoprotection

Vitamin D is produced in the skin by ultraviolet (UV) B radiation (290-320 nm). The active metabolite 1,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3] is made systemically by hydroxylation of vitamin D in the liver and the kidney, but also locally in the epidermis, which suggests that 1,25(OH)(2)D-3 may have important functions in the skin. 1,25(OH)(2)D-3 has opposing effects: it can mimic immunosuppressive effects caused by UV irradiation in some models, or reverse UV-induced DNA damage and immunosuppression in other models. 1,25(OH)(2)D-3 exerts effects on Langerhans cells that are characteristic of those associated with UV radiation (UVR)-induced suppression of contact hypersensitivity, and topical application of the vitamin D analogue calcipotriene suppresses contact hypersensitivity in human subjects to a similar extent as UVR. However, 1,25(OH)(2)D-3 decreases DNA damage both in vitro when added to human skin cells in culture before and after UVR, and in vivo when applied to mouse skin after UVR. Furthermore, topical 1,25(OH)(2)D-3 applied to mouse skin after UVR reversed the immunosuppressive effect of UVR in a contact hypersensitivity model. This review will discuss the role of 1,25(OH)(2)D-3 as either a mediator of UVR-induced immune suppression or as a photoprotective molecule against UVR-induced DNA damage and immune suppression.