title: Cationic antimicrobial peptides in psoriatic skin cooperate to break innate tolerance to self-DNA.
abstract: Psoriasis is a T-cell-mediated skin autoimmune disease characterized by the aberrant activation of dermal dendritic cells (DCs) and the sustained epidermal expression of antimicrobial peptides. We have previously identified a link between these two events by showing that the cathelicidin antimicrobial peptide LL37 has the ability to trigger self-nucleic acid mediated activation of plasmacytoid DCs (pDCs) in psoriatic skin. Whether other cationic antimicrobial peptides exert similar activities is unknown. By analyzing heparin-binding HPLC fractions of psoriatic scales, we found that human beta-defensin (hBD)2, hBD3, and lysozyme are additional triggers of pDC activation in psoriatic skin lesions. Like LL37, hBD2, hBD3, and lysozyme are able to condense self-DNA into particles that are endocytosed by pDCs, leading to activation of TLR9. In contrast, other antimicrobial peptides expressed in psoriatic skin including elafin, hBD1, and psoriasin (S100A7) did not show similar activities. hBD2, hBD3, and lysozyme were detected in psoriatic skin lesions in the vicinity of pDCs and found to cooperate with LL37 to induce high levels of IFN production by pDCs, suggesting their concerted role in the pathogenesis of psoriasis.
authors.affiliation: Department of Dermatology, University Hospital of Lausanne CHUV, Lausanne, Switzerland; Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Lande
authors.forename: Georgios
authors.initials: G
authors.lastname: Chamilos
authors.forename: Dipyaman
authors.initials: D
authors.lastname: Ganguly
authors.forename: Olivier
authors.initials: O
authors.lastname: Demaria
authors.forename: Loredana
authors.initials: L
authors.lastname: Frasca
authors.forename: Sophie
authors.initials: S
authors.lastname: Durr
authors.forename: Curdin
authors.initials: C
authors.lastname: Conrad
authors.forename: Jens
authors.initials: J
authors.lastname: Schröder
authors.forename: Michel
authors.initials: M
authors.lastname: Gilliet
mesh_terms: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins / Q000235:genetics / Q000276:immunology; D004247:DNA / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D007801:Langerhans Cells / Q000276:immunology* / Q000473:pathology; D009113:Muramidase / Q000235:genetics / Q000276:immunology*; D011565:Psoriasis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D017634:Self Tolerance; D015398:Signal Transduction; D012867:Skin / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000276:immunology; D023083:beta-Defensins / Q000235:genetics / Q000276:immunology*
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; C422950:DEFB103A protein, human; C106641:DEFB4A protein, human; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D023083:beta-Defensins; D004247:DNA; D009113:Muramidase
keywords: Antimicrobial peptides; Plasmacytoid DC; Psoriasis; Skin; Toll-like receptor