title: Dynamic Changes in Resident and Infiltrating Epidermal Dendritic Cells in Active and Resolved Psoriasis.
abstract: Epidermal Langerhans cells (LCs) are spatially separated from dermal dendritic cells (DCs) in healthy human skin. In active psoriasis, maintained by local production of IL-23 and IL-17, inflammatory DCs infiltrate both skin compartments. Here we show that CCR2+epidermal DCs (eDCs) were confined to lesional psoriasis and phenotypically distinct from dermal DCs. The eDCs exceeded the number of LCs and displayed high expression of genes involved in neutrophil recruitment and the activation of keratinocytes and T cells. Resident LCs responded to toll-like receptor 4 and toll-like receptor 7/8 activation with increased IL-23 production, whereas eDCs additionally produced IL-1β together with IL-23 and tumor necrosis factor. Psoriasis typically recur in fixed skin lesions. eDCs were absent from resolved psoriasis. Instead, LCs from anti-tumor necrosis factor-treated lesions retained high IL23A expression and responded to toll-like receptor stimulation by producing IL-23. Our results reveal phenotypic and functional properties of eDCs and resident LCs in different clinical phases of psoriasis, and the capacity of these cells to amplify the epidermal microenvironment through the secretion of IL-17 polarizing cytokines.
authors.affiliation: Department of Dermatology, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Elisa
authors.initials: E
authors.lastname: Martini
authors.affiliation: Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Wikén
authors.affiliation: Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Stanley
authors.initials: S
authors.lastname: Cheuk
authors.affiliation: Department of Dermatology, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Irène
authors.initials: I
authors.lastname: Gallais Sérézal
authors.affiliation: Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Faezzah
authors.initials: F
authors.lastname: Baharom
authors.affiliation: Department of Dermatology, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Mona
authors.initials: M
authors.lastname: Ståhle
authors.affiliation: Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Smed-Sörensen
authors.affiliation: Department of Dermatology, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. Electronic address: liv.eidsmo@ki.se.
authors.forename: Liv
authors.initials: L
authors.lastname: Eidsmo
mesh_terms: D001707:Biopsy, Needle; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology* / Q000648:ultrastructure; D000078404:Epidermal Cells; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000378:metabolism; D053759:Interleukin-23 / Q000378:metabolism; D007801:Langerhans Cells / Q000166:cytology* / Q000648:ultrastructure; D018613:Microscopy, Confocal / Q000379:methods; D011565:Psoriasis / Q000276:immunology / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012016:Reference Values; D012494:Sampling Studies; D018709:Statistics, Nonparametric; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D016207:Cytokines; D020381:Interleukin-17; D053759:Interleukin-23; D051193:Toll-Like Receptors