title: 1,25-dihydroxyvitamin D exerts similar immunosuppressive effects as UVR but is dispensable for local UVR-induced immunosuppression.
abstract: 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 1α,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.
authors.affiliation: Department of Dermatology, University of Kiel, Kiel, Germany.
authors.forename: Agatha
authors.initials: A
authors.lastname: Schwarz
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Navid
authors.forename: Tim
authors.initials: T
authors.lastname: Sparwasser
authors.forename: Björn E
authors.initials: BE
authors.lastname: Clausen
authors.forename: Thomas
authors.initials: T
authors.lastname: Schwarz
mesh_terms: D000287:Administration, Topical; D019264:Adoptive Transfer; D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology; D003877:Dermatitis, Contact / Q000188:drug therapy* / Q000276:immunology / Q000532:radiotherapy*; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology; D007166:Immunosuppressive Agents / Q000276:immunology* / Q000494:pharmacology; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology; D037241:Mannose-Binding Lectins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018167:Receptors, Calcitriol / Q000235:genetics / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D014466:Ultraviolet Rays; D014467:Ultraviolet Therapy / Q000379:methods*; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000276:immunology / Q000494:pharmacology
chemical_list: D000954:Antigens, Surface; C498497:Cd207 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007166:Immunosuppressive Agents; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D018167:Receptors, Calcitriol; D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D