title: Specific roles for dendritic cell subsets during initiation and progression of psoriasis.
abstract: Several subtypes of APCs are found in psoriasis patients, but their involvement in disease pathogenesis is poorly understood. Here, we investigated the contribution of Langerhans cells (LCs) and plasmacytoid DCs (pDCs) in psoriasis. In human psoriatic lesions and in a psoriasis mouse model (DKO* mice), LCs are severely reduced, whereas pDCs are increased. Depletion of pDCs in DKO* mice prior to psoriasis induction resulted in a milder phenotype, whereas depletion during active disease had no effect. In contrast, while depletion of Langerin-expressing APCs before disease onset had no effect, depletion from diseased mice aggravated psoriasis symptoms. Disease aggravation was due to the absence of LCs, but not other Langerin-expressing APCs. LCs derived from DKO* mice produced increased IL-10 levels, suggesting an immunosuppressive function. Moreover, IL-23 production was high in psoriatic mice and further increased in the absence of LCs. Conversely, pDC depletion resulted in reduced IL-23 production, and therapeutic inhibition of IL-23R signaling ameliorated disease symptoms. Therefore, LCs have an anti-inflammatory role during active psoriatic disease, while pDCs exert an instigatory function during disease initiation.
authors.affiliation: Department of Medicine I, Comprehensive Cancer Center Institute of Cancer Research Medical University of Vienna, Vienna, Austria.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Glitzner
authors.affiliation: Department of Medicine I, Comprehensive Cancer Center Institute of Cancer Research Medical University of Vienna, Vienna, Austria.
authors.forename: Ana
authors.initials: A
authors.lastname: Korosec
authors.affiliation: Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, Medical University of Vienna, Vienna, Austria.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Brunner
authors.affiliation: Department of Medicine I, Comprehensive Cancer Center Institute of Cancer Research Medical University of Vienna, Vienna, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Drobits
authors.affiliation: Department of Medicine I, Comprehensive Cancer Center Institute of Cancer Research Medical University of Vienna, Vienna, Austria.
authors.forename: Nicole
authors.initials: N
authors.lastname: Amberg
authors.affiliation: BBVA Foundation-CNIO Cancer Cell Biology Programme Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
authors.forename: Helia B
authors.initials: HB
authors.lastname: Schonthaler
authors.affiliation: Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, Medical University of Vienna, Vienna, Austria.
authors.forename: Tamara
authors.initials: T
authors.lastname: Kopp
authors.affiliation: BBVA Foundation-CNIO Cancer Cell Biology Programme Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
authors.forename: Erwin F
authors.initials: EF
authors.lastname: Wagner
authors.affiliation: Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, Medical University of Vienna, Vienna, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Stingl
authors.affiliation: Department of Medicine I, Comprehensive Cancer Center Institute of Cancer Research Medical University of Vienna, Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Holcmann
authors.affiliation: Department of Medicine I, Comprehensive Cancer Center Institute of Cancer Research Medical University of Vienna, Vienna, Austria maria.sibilia@meduniwien.ac.at.
authors.forename: Maria
authors.initials: M
authors.lastname: Sibilia
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D016026:Bone Marrow Transplantation; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D018450:Disease Progression; D005434:Flow Cytometry; D006801:Humans; D000077271:Imiquimod; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D053759:Interleukin-23 / Q000276:immunology / Q000378:metabolism; D007801:Langerhans Cells / Q000276:immunology* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D016755:Proto-Oncogene Proteins c-jun / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D011565:Psoriasis / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D018123:Receptors, Interleukin / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D012867:Skin / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D000911:Antibodies, Monoclonal; D053759:Interleukin-23; C584097:JunB protein, mouse; D016755:Proto-Oncogene Proteins c-jun; D018123:Receptors, Interleukin; D014157:Transcription Factors; C528688:interleukin-23 receptor, mouse; D016753:Interleukin-10; D000077271:Imiquimod
keywords: AP‐1; IL‐23; Langerhans cells; plasmacytoid dendritic cells; psoriasis