1,25-Dihydroxyvitamin D Exerts Similar Immunosuppressive Effects as UVR but Is Dispensable for Local UVR-Induced Immunosuppression

Low-dose UV radiation (UVR) inhibits the induction of contact hypersensitivity and induces regulatory T cells (Tregs), which because of their antigen specificity harbor therapeutic potential. Topical application of 1 alpha,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3) is known to induce Tregs as well, which implies that 1,25(OH)(2)D-3 might be involved in UVR-induced immunosuppression. It was the aim of this study to clarify this issue, to further characterize 1,25(OH)(2)D-3-induced Tregs and to determine whether they differ from UVR-induced Tregs. Our data demonstrate that 1,25(OH)(2)D-3-induced Tregs act in an antigen-specific manner and belong to the Foxp3-expressing subtype of Tregs as demonstrated by diphtheria toxin (DT)-mediated depletion of Foxp3(+) Tregs in DEREG (depletion of Tregs) mice. Using Langerin-DTR (DT receptor) knock-in mice, it was shown that Langerhans cells (LCs) are required for the induction of Tregs by 1,25(OH)(2)D-3, as depletion of LCs but not Langerin(+) dermal dendritic cells abrogated the induction of Tregs. Taken together, 1,25(OH)(2)D-3 affects the immune system in a similar manner as UVR, probably using the same pathways. However, vitamin D receptor knockout mice were equally susceptible to UVR-induced immunosupppression as wild-type controls. This indicates that 1,25(OH)(2)D-3 exerts similar immunosuppressive effects as UVR but is dispensable for local UVR-induced immunosuppression. Journal of Investigative Dermatology (2012) 132, 2762-2769; doi:10.1038/jid.2012.238; published online 2 August 2012