title: Vitamin D controls murine and human plasmacytoid dendritic cell function.
abstract: Topical application of the vitamin D (VitD) analog calcipotriol is a highly effective standard treatment modality of psoriatic skin lesions. However, the immune modulatory effects of the treatment are incompletely understood. VitD is well known to induce tolerogenic responses in conventional dendritic cells (cDCs). Plasmacytoid DCs (pDCs) comprise a specialized, naturally occurring DC subset known to be important in autoimmune diseases including psoriasis. pDCs from the blood rapidly infiltrate psoriatic skin and are key to the initiation of the immune-mediated pathogenesis of the disease. We now demonstrate that pDCs express various proteins of the VitD receptor (VDR) pathway, including the VitD-metabolizing enzymes Cyp27B1 and Cyp24A1, and that VDR is transcriptionally active in pDCs. Moreover, VitD impairs the capacity of murine and human pDCs to induce T-cell proliferation and secretion of the T-helper 1 cytokine IFNγ. The inhibitory effect of VitD is dependent on the expression of the VDR in the DCs. This study demonstrates that VitD signaling can act as a natural inhibitory mechanism on both cDCs and pDCs, which may instigate the development of VitD-based therapeutic applications for psoriasis and other inflammatory skin diseases.
authors.affiliation: Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Nina
authors.initials: N
authors.lastname: Karthaus
authors.affiliation: Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Annemiek B
authors.initials: AB
authors.lastname: van Spriel
authors.affiliation: Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Maaike W G
authors.initials: MWG
authors.lastname: Looman
authors.affiliation: Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Shuo
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Lisanne M
authors.initials: LM
authors.lastname: Spilgies
authors.affiliation: Department of Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium.
authors.forename: Liesbet
authors.initials: L
authors.lastname: Lieben
authors.affiliation: Department of Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Carmeliet
authors.affiliation: Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Marleen
authors.initials: M
authors.lastname: Ansems
authors.affiliation: Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands. Electronic address: G.Adema@ncmls.ru.nl.
authors.forename: Gosse J
authors.initials: GJ
authors.lastname: Adema
mesh_terms: D000818:Animals; D002112:Calcifediol / Q000494:pharmacology; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D003879:Dermatologic Agents / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011565:Psoriasis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018167:Receptors, Calcitriol / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014807:Vitamin D / Q000276:immunology* / Q000494:pharmacology
chemical_list: D003879:Dermatologic Agents; D018167:Receptors, Calcitriol; C579457:VDR protein, human; D014807:Vitamin D; C055085:calcipotriene; D007371:Interferon-gamma; D002117:Calcitriol; D002112:Calcifediol