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.
MeSH terms
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Case-Control Studies
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Cells, Cultured
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Cytokines / metabolism
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Cytosol / metabolism*
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Cytosol / pathology
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DNA / metabolism*
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Dermatitis / genetics
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Dermatitis / metabolism
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Dermatitis / pathology*
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Humans
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Keratinocytes / metabolism
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Keratinocytes / pathology
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Psoriasis / genetics
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Psoriasis / metabolism
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Psoriasis / pathology*
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RNA / metabolism*
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RNA-Directed DNA Polymerase / metabolism*
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Skin / metabolism
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Skin / pathology*
Substances
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Cytokines
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RNA
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DNA
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RNA-Directed DNA Polymerase
Grants and funding
This study was funded by the Société de Recherche Dermatologique and by the Société Française de Dermatologie. The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript.