title: Monocyte-derived inflammatory Langerhans cells and dermal dendritic cells mediate psoriasis-like inflammation.
abstract: Dendritic cells (DCs) have been implicated in the pathogenesis of psoriasis but the roles for specific DC subsets are not well defined. Here we show that DCs are required for psoriasis-like changes in mouse skin induced by the local injection of IL-23. However, Flt3L-dependent DCs and resident Langerhans cells are dispensable for the inflammation. In epidermis and dermis, the critical DCs are TNF-producing and IL-1β-producing monocyte-derived DCs, including a population of inflammatory Langerhans cells. Depleting Ly6Chiblood monocytes reduces DC accumulation and the skin changes induced either by injecting IL-23 or by application of the TLR7 agonist imiquimod. Moreover, we find that IL-23-induced inflammation requires expression of CCR6 by DCs or their precursors, and that CCR6 mediates monocyte trafficking into inflamed skin. Collectively, our results imply that monocyte-derived cells are critical contributors to psoriasis through production of inflammatory cytokines that augment the activation of skin T cells.
authors.affiliation: Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Tej Pratap
authors.initials: TP
authors.lastname: Singh
authors.affiliation: Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Howard H
authors.initials: HH
authors.lastname: Zhang
authors.affiliation: Institute of Pathophysiology and Immunology, Medical University of Graz, 8010 Graz, Austria.
authors.forename: Izabela
authors.initials: I
authors.lastname: Borek
authors.affiliation: Department of Dermatology, Medical University of Graz, A-8036 Graz, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Wolf
authors.affiliation: Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Hedrick
authors.affiliation: Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Satya P
authors.initials: SP
authors.lastname: Singh
authors.affiliation: Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Kelsall
authors.affiliation: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany.
authors.forename: Bjorn E
authors.initials: BE
authors.lastname: Clausen
authors.affiliation: Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Farber
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology; D000634:Aminoquinolines / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D003713:Dendritic Cells / Q000502:physiology*; D003875:Drug Eruptions; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D000077271:Imiquimod; D007249:Inflammation / Q000139:chemically induced*; D053759:Interleukin-23 / Q000008:administration & dosage / Q000494:pharmacology; D007801:Langerhans Cells / Q000145:classification / Q000502:physiology*; D008285:Major Histocompatibility Complex; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000502:physiology*; D011565:Psoriasis / Q000473:pathology*; D012867:Skin / Q000166:cytology*
chemical_list: D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D053759:Interleukin-23; D008565:Membrane Proteins; C084881:flt3 ligand protein; D000077271:Imiquimod