title: Cytosolic RNA:DNA Duplexes Generated by Endogenous Reverse Transcriptase Activity as Autonomous Inducers of Skin Inflammation in Psoriasis.
abstract: Psoriasis is a chronic skin disease of unknown ætiology. Recent studies suggested that a large amount of cytosolic DNA (cyDNA) in keratinocytes is breaking keratinocytes DNA tolerance and promotes self-sustained inflammation in the psoriatic lesion. We investigated the origin of this cyDNA. We show that, amongst all the possible DNA structures, the cyDNA could be present as RNA:DNA duplexes in keratinocytes. We further show that endogenous reverse transcriptase activities generate such duplexes and consequently activate the production of Th1-inflammatory cytokines. These observations open a new research avenue related to endogenous retroelements for the aetiology of psoriasis and probably of other human chronic inflammatory diseases.
authors.affiliation: Inserm UMR 1058, Montpellier, France.|Etablissement Français du Sang, Montpellier, France.|University of Montpellier, Montpellier, France.
authors.forename: Jean-Pierre
authors.identifier: http://orcid.org/0000-0002-6863-6350
authors.initials: JP
authors.lastname: Molès
authors.affiliation: Inserm UMR 1058, Montpellier, France.|Etablissement Français du Sang, Montpellier, France.|University of Montpellier, Montpellier, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Griez
authors.affiliation: University of Montpellier, Montpellier, France.|CHU of Montpellier, Montpellier, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Guilhou
authors.affiliation: Inserm UMR 1058, Montpellier, France.|Etablissement Français du Sang, Montpellier, France.|University of Montpellier, Montpellier, France.|CHU of Montpellier, Montpellier, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Girard
authors.affiliation: Inserm UMR 1058, Montpellier, France.|Etablissement Français du Sang, Montpellier, France.|University of Montpellier, Montpellier, France.|CHU of Montpellier, Montpellier, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Nagot
authors.affiliation: Inserm UMR 1058, Montpellier, France.|Etablissement Français du Sang, Montpellier, France.|University of Montpellier, Montpellier, France.|CHU of Montpellier, Montpellier, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Van de Perre
authors.affiliation: Inserm UMR 1058, Montpellier, France.|Etablissement Français du Sang, Montpellier, France.|University of Montpellier, Montpellier, France.|CHU of Montpellier, Montpellier, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Dujols
mesh_terms: D016022:Case-Control Studies; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism* / Q000473:pathology; D004247:DNA / Q000378:metabolism*; D003872:Dermatitis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D011565:Psoriasis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012313:RNA / Q000378:metabolism*; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism*; D012867:Skin / Q000378:metabolism / Q000473:pathology*
chemical_list: D016207:Cytokines; D012313:RNA; D004247:DNA; D012194:RNA-Directed DNA Polymerase