title: Intradermal application of vitamin D3 increases migration of CD14+ dermal dendritic cells and promotes the development of Foxp3+ regulatory T cells.
abstract: The active form of vitamin D3 (VitD) is a potent immunosuppressive drug. Its effects are mediated in part through dendritic cells (DCs) that promote the development of regulatory T cells (Tregs). However, it remains elusive how VitD would influence the different human skin DC subsets, e.g., CD1a(+)/langerin(+) Langerhans cells, CD14(+) DDCs and CD1a(+) DDCs upon administration through the skin route in their natural environment. We addressed this issue by intradermal (ID) administration of VitD in a human skin explant system that closely resembles physiological conditions. ID injection of VitD selectively enhanced the migration of CD14(+) DDCs, a subset known for the induction of tolerance. Moreover, ID injection of VitD repressed the LPS-induced T cell stimulatory capacity of migrating DCs. These migrating DCs collectively induced T cells with suppressive activity and abolished IFN-γ productivity. Those induced T cells were characterized by the expression of Foxp3. Thus, we report the novel finding that ID injection of VitD not only modifies skin DC migration, but also programs these DCs in their natural milieu to promote the development of Foxp3(+) Tregs.
authors.affiliation: Department of Cell Biology & Histology; Academic Medical Center; Amsterdam, the Netherlands; Current address: Department of Tumor Immunology; Nijmegen Centre for Molecular Life Sciences and Radboud University Nijmegen Medical Centre; Nijmegen, the Netherlands.
authors.forename: Ghaith
authors.initials: G
authors.lastname: Bakdash
authors.forename: Laura P
authors.initials: LP
authors.lastname: Schneider
authors.forename: Toni M M
authors.initials: TM
authors.lastname: van Capel
authors.forename: Martien L
authors.initials: ML
authors.lastname: Kapsenberg
authors.forename: Marcel B M
authors.initials: MB
authors.lastname: Teunissen
authors.forename: Esther C
authors.initials: EC
authors.lastname: de Jong
mesh_terms: D002465:Cell Movement; D002762:Cholecalciferol / Q000008:administration & dosage*; D051858:Forkhead Transcription Factors / Q000032:analysis*; D006801:Humans; D007271:Injections, Intradermal; D007371:Interferon-gamma / Q000378:metabolism; D007801:Langerhans Cells / Q000187:drug effects / Q000276:immunology* / Q000502:physiology*; D018950:Lipopolysaccharide Receptors / Q000032:analysis*; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000276:immunology*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D018950:Lipopolysaccharide Receptors; D002762:Cholecalciferol; D007371:Interferon-gamma
keywords: intradermal injection; regulatory T cells; skin dendritic cells; tolerance; vitamin D