title: Dynamics and Transcriptomics of Skin Dendritic Cells and Macrophages in an Imiquimod-Induced, Biphasic Mouse Model of Psoriasis.
abstract: Psoriasis is a chronic inflammatory skin disease of unknown etiology. Previous studies showed that short-term, 5-7 d-long application of imiquimod (IMQ), a TLR7 agonist, to the skin of mice triggers a psoriasis-like inflammation. In the current study, by applying IMQ for 14 consecutive d, we established an improved mouse psoriasis-like model in that it recapitulated many of the clinical and cellular hallmarks observed in human patients during both the early-onset and the late-stable phase of psoriasis. Although macrophages and dendritic cells (DCs) have been proposed to drive the psoriatic cascade, their largely overlapping phenotype hampered studying their respective role. Based on our ability to discriminate Langerhans cells (LCs), conventional DCs, monocytes, monocyte-derived DCs, macrophages, and plasmacytoid DCs in the skin, we addressed their dynamics during both phases of our biphasic psoriasis-like model. Plasmacytoid DCs were not detectable during the whole course of IMQ treatment. During the early phase, neutrophils infiltrated the epidermis, whereas monocytes and monocyte-derived DCs were predominant in the dermis. During the late phase, LCs and macrophage numbers transiently increased in the epidermis and dermis, respectively. LC expansion resulted from local proliferation, a conclusion supported by global transcriptional analysis. Genetic depletion of LCs permitted to evaluate their function during both phases of the biphasic psoriasis-like model and demonstrated that their absence resulted in a late phase that is associated with enhanced neutrophil infiltration. Therefore, our data support an anti-inflammatory role of LCs during the course of psoriasis-like inflammation.
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, INSERM, U1104, CNRS UMR7280, 13288 Marseille, France; and Department of Dermatology, Charité University Medicine Berlin, 10117 Berlin, Germany.
authors.forename: Dorothea
authors.initials: D
authors.lastname: Terhorst
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, INSERM, U1104, CNRS UMR7280, 13288 Marseille, France; and.
authors.forename: Rabie
authors.initials: R
authors.lastname: Chelbi
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, INSERM, U1104, CNRS UMR7280, 13288 Marseille, France; and.
authors.forename: Christian
authors.initials: C
authors.lastname: Wohn
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, INSERM, U1104, CNRS UMR7280, 13288 Marseille, France; and.
authors.forename: Camille
authors.initials: C
authors.lastname: Malosse
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, INSERM, U1104, CNRS UMR7280, 13288 Marseille, France; and.
authors.forename: Samira
authors.initials: S
authors.lastname: Tamoutounour
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, INSERM, U1104, CNRS UMR7280, 13288 Marseille, France; and.
authors.forename: Audrey
authors.identifier: http://orcid.org/0000-0001-6956-5411
authors.initials: A
authors.lastname: Jorquera
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, INSERM, U1104, CNRS UMR7280, 13288 Marseille, France; and.
authors.forename: Marc
authors.initials: M
authors.lastname: Bajenoff
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, INSERM, U1104, CNRS UMR7280, 13288 Marseille, France; and.
authors.forename: Marc
authors.identifier: http://orcid.org/0000-0002-6436-7966
authors.initials: M
authors.lastname: Dalod
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, INSERM, U1104, CNRS UMR7280, 13288 Marseille, France; and bernardm@ciml.univ-mrs.fr henri@ciml.univ-mrs.fr.
authors.forename: Bernard
authors.identifier: http://orcid.org/0000-0003-1340-9342
authors.initials: B
authors.lastname: Malissen
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, INSERM, U1104, CNRS UMR7280, 13288 Marseille, France; and bernardm@ciml.univ-mrs.fr henri@ciml.univ-mrs.fr.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Henri
mesh_terms: D000634:Aminoquinolines / Q000009:adverse effects* / Q000494:pharmacology; D000818:Animals; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D000077271:Imiquimod; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D011565:Psoriasis / Q000139:chemically induced* / Q000276:immunology* / Q000473:pathology; D012867:Skin / Q000276:immunology* / Q000473:pathology; D059467:Transcriptome / Q000187:drug effects*
chemical_list: D000634:Aminoquinolines; D000077271:Imiquimod